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a [histone H3]-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
a [histone H3]-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
?
ATKAARK(me3)-SAPATGGVKKPHRYRPG-GK(biotin) + 2-oxoglutarate + O2
ATKAARKSAPATGGVKKPHRYRPG-GK(biotin) + succinate + formaldehyde + CO2
usage of immunodetection for assay quantification
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?
dimethyl-histone 3 L-lysine 36 + 2-oxoglutarate + O2
methyl-histone 3 L-lysine 36 + succinate + formaldehyde + CO2
-
enzyme Rph1 is specific for di- and trimethyl-histone 3 L-lysine36
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-
?
histone H3 N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
histone H3 N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
histone H3 N6-methyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 L-lysine36 + succinate + formaldehyde + CO2
histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
trimethyl-histone 3 L-lysine 36 + 2-oxoglutarate + O2
dimethyl-histone 3 L-lysine 36 + succinate + formaldehyde + CO2
-
enzyme Rph1 is specific for di- and trimethyl-histone 3 L-lysine36
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-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 26 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 26 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 26 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine26 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
[histone H3]-N6,N6,N6-trimethyllysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-lysine36 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-N6-methyllysine36 + 2 succinate + 2 formaldehyde + 2 CO2
[histone H3]-N6,N6,N6-trimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyllysine36 + succinate + formaldehyde + CO2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
[histone H3]-N6,N6-dimethyl-L-lysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine36 + 2 succinate + 2 formaldehyde + 2 CO2
[histone H3]-N6,N6-dimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-lysine36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6-methyllysine36 + succinate + formaldehyde + CO2
additional information
?
-
histone H3 N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
calf thymus type II-A histones
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-
?
histone H3 N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
calf thymus type II-A histones
-
-
?
histone H3 N6-methyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 L-lysine36 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6-methyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 L-lysine36 + succinate + formaldehyde + CO2
calf thymus type II-A histones
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-
?
histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
-
?
histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
-
KDM4A demethylates H3K36me3, a modification enriched in the 3' end of active genes
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?
histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
-
?
histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
-
?
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
-
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
substrate binding structure, overview
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-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-N6-methyllysine36 + 2 succinate + 2 formaldehyde + 2 CO2
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-
-
?
[histone H3]-N6,N6,N6-trimethyllysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-N6-methyllysine36 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-N6-methyllysine36 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyllysine36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyllysine36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyllysine36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyllysine36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
substrate binding structure, overview
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-
?
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
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-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine36 + 2 succinate + 2 formaldehyde + 2 CO2
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-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine36 + 2 succinate + 2 formaldehyde + 2 CO2
histone H3K36 methylation is enriched in coding regions of actively transcribed genes. dKDM4A is a JmjC domain-containing protein specifically demethylates H3K36me2 and H3K36me3 both in vitro and in vivo. H3K36 methylation is also subject to dynamic regulation. HP1a regulates histone H3K36 methylation in Drosophila larvae
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?
[histone H3]-N6,N6-dimethyl-L-lysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine36 + 2 succinate + 2 formaldehyde + 2 CO2
-
JmjC domain-containing protein dKDM4A is a histone H3K36 demethylase. Histone H3 methylation is one of the consistent marks distinguishing alternative chromatin packaging states
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[histone H3]-N6,N6-dimethyl-L-lysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine36 + 2 succinate + 2 formaldehyde + 2 CO2
with HeLa cell core histone 3. dKDM4A is a JmjC domain-containing protein specifically demethylates H3K36me2 and H3K36me3 both in vitro and in vivo. The demethylation reaction mediated by dKDM4A requires Fe2+, 2-oxoglutarate, and ascorbate as cofactors
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[histone H3]-N6,N6-dimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6-methyllysine36 + succinate + formaldehyde + CO2
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?
[histone H3]-N6,N6-dimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6-methyllysine36 + succinate + formaldehyde + CO2
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-
-
?
[histone H3]-N6,N6-dimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6-methyllysine36 + succinate + formaldehyde + CO2
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?
additional information
?
-
the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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?
additional information
?
-
the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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?
additional information
?
-
the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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?
additional information
?
-
the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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?
additional information
?
-
the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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?
additional information
?
-
the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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additional information
?
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HP1a and dKDM4A interact with each other and loss of HP1a leads to an increased level of histone H3K36me3
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additional information
?
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HP1a and dKDM4A interact with each other and loss of HP1a leads to an increased level of histone H3K36me3
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additional information
?
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dJMJD2(1)/CG15835 is capable of demethylating H3K9me3 and H3K36me3
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additional information
?
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dJMJD2(1)/CG15835 is capable of demethylating H3K9me3 and H3K36me3
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additional information
?
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dJMJD2(2)/CG33182 is capable of demethylating H3K9me3 and H3K36me3
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additional information
?
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dJMJD2(2)/CG33182 is capable of demethylating H3K9me3 and H3K36me3
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additional information
?
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the bifunctional enzyme specifically demethylates Lys9 (EC 1.14.11.66) and Lys36 residues of histone H3
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additional information
?
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JmjD2A is specific for H3K9me3 and H3K36me3 substrates. JmjD2A directly binds to regulatory regions of neural crest specifier genes in vivo
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additional information
?
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JmjD2A is specific for H3K9me3 and H3K36me3 substrates
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additional information
?
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JMJD2A also catalyzes the reaction of the [histone H3]-lysine-9 demethylase. JMJD2A exclusively catalyzes the demethylation of H3K9me3 and H3K36me3, converting H3K9/36me3 to H3K9/36me2 but it cannot convert H3K9/36me1 or unmethylated H3K9/K36, overview
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additional information
?
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bifunctional H3K9/36me3 lysine demethylase KDM4A/JMJD2A acting on Lys 9 and Lys36 of histone 3
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additional information
?
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JMJD2A demethylates trimethylated histone K9/K36 to di- but not mono- or unmethylated products, i.e. JMJD2A also catalyzes the reactions of EC 1.14.11.66, H3K9 trimethyl demethylase
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additional information
?
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bifunctional enzyme active on H3K9me3/me2 (EC 1.14.11.66) and on H3K36me3/me2
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additional information
?
-
bifunctional KDM4A catalyzes demethylation of tri- and di-methylated forms of both histone H3 lysine 9 (H3K9me3/me2) and lysine 36 (H3K36me3/me2). Enzyme KDM4A preferentially catalyzes demethylation at Lys9 rather than Lys36 under identical conditions. Demethylation of H3K9me3 to H3K9me0 is observed on prolonged incubation of 15-residue H3K9me3 peptides
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?
additional information
?
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bifunctional KDM4A catalyzes demethylation of tri- and di-methylated forms of both histone H3 lysine 9 (H3K9me3/me2) and lysine 36 (H3K36me3/me2). Enzyme KDM4A preferentially catalyzes demethylation at Lys9 rather than Lys36 under identical conditions. Demethylation of H3K9me3 to H3K9me0 is observed on prolonged incubation of 15-residue H3K9me3 peptides
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additional information
?
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bifunctional KDM4A catalyzes demethylation of tri- and di-methylated forms of both histone H3 lysine 9 (H3K9me3/me2) and lysine 36 (H3K36me3/me2). Enzyme KDM4A preferentially catalyzes demethylation at Lys9 rather than Lys36 under identical conditions. Demethylation of H3K9me3 to H3K9me0 is observed on prolonged incubation of 15-residue H3K9me3 peptides
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additional information
?
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bifunctional KDM4A catalyzes demethylation of tri- and di-methylated forms of both histone H3 lysine 9 (H3K9me3/me2) and lysine 36 (H3K36me3/me2). Enzyme KDM4B preferentially catalyzes demethylation at Lys9 rather than Lys36 under identical conditions. Demethylation of H3K9me3 to H3K9me0 is observed on prolonged incubation of 15-residue H3K9me3 peptides
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additional information
?
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bifunctional KDM4A catalyzes demethylation of tri- and di-methylated forms of both histone H3 lysine 9 (H3K9me3/me2) and lysine 36 (H3K36me3/me2). Enzyme KDM4B preferentially catalyzes demethylation at Lys9 rather than Lys36 under identical conditions. Demethylation of H3K9me3 to H3K9me0 is observed on prolonged incubation of 15-residue H3K9me3 peptides
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additional information
?
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bifunctional KDM4A catalyzes demethylation of tri- and di-methylated forms of both histone H3 lysine 9 (H3K9me3/me2) and lysine 36 (H3K36me3/me2). Enzyme KDM4B preferentially catalyzes demethylation at Lys9 rather than Lys36 under identical conditions. Demethylation of H3K9me3 to H3K9me0 is observed on prolonged incubation of 15-residue H3K9me3 peptides
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additional information
?
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bifunctional KDM4A catalyzes demethylation of tri- and di-methylated forms of both histone H3 lysine 9 (H3K9me3/me2) and lysine 36 (H3K36me3/me2). Enzyme KDM4C preferentially catalyzes demethylation at Lys9 rather than Lys36 under identical conditions. Demethylation of H3K9me3 to H3K9me0 is observed on prolonged incubation of 15-residue H3K9me3 peptides
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additional information
?
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bifunctional KDM4A catalyzes demethylation of tri- and di-methylated forms of both histone H3 lysine 9 (H3K9me3/me2) and lysine 36 (H3K36me3/me2). Enzyme KDM4C preferentially catalyzes demethylation at Lys9 rather than Lys36 under identical conditions. Demethylation of H3K9me3 to H3K9me0 is observed on prolonged incubation of 15-residue H3K9me3 peptides
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additional information
?
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bifunctional KDM4A catalyzes demethylation of tri- and di-methylated forms of both histone H3 lysine 9 (H3K9me3/me2) and lysine 36 (H3K36me3/me2). Enzyme KDM4C preferentially catalyzes demethylation at Lys9 rather than Lys36 under identical conditions. Demethylation of H3K9me3 to H3K9me0 is observed on prolonged incubation of 15-residue H3K9me3 peptides
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additional information
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enzyme additionally demethylates H3K9me3, reaction of EC 1.14.11.66
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additional information
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human enzyme JMJD2A (jumonji domain containing 2A) is selective towards tri- and dimethylated histone H3 lysyl residues 9 and 36 (H3K9me3/me2 and H3K36me3/me2), it discriminates between methylation states and achieves sequence selectivity for H3K9. Structures reveal a lysyl-binding pocket in which substrates are bound in distinct bent conformations involving the Zn2+-binding site
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additional information
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human JMJD2A exhibits dual specificity for the trimethylated and, to a lesser extent, the dimethylated forms of H3K9 and H3K36, with an approximately fivefold preference in specificity for the H3K9me3 substrate due to a higher KM value for the H3K36me3 peptide, suggesting that JMJD2A preferentially recognizes the H3K9me3 site
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additional information
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JHDM3A removes the me3 group from modified H3 lysine 9 (H3K9) and H3 lysine 36 (H3K36)
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additional information
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JMJD2A is a JmjC histone demethylase (HDM) that catalyzes the demethylation of di- and trimethylated Lys9 and Lys36 in histone H3 (H3K9me2/3 and H3K36me2/3). Trimethylated Lys9 is the best substrate. JMJD2A preferentially demethylates trimethylated substrates. Histone substrates are recognized through a network of backbone hydrogen bonds and hydrophobic interactions that deposit the trimethyllysine into the active site. The trimethylated epsilon-ammonium cation is coordinated within a methylammonium-binding pocket through carbon-oxygen hydrogen bonds that position one of the zeta-methyl groups adjacent to the Fe(II) center for hydroxylation and demethylation. Analysis of the H3K9me3 or H3K36me3 peptide binding structure to the enzyme, overview
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additional information
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the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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additional information
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the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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additional information
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the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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additional information
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the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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additional information
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the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates. Usage of a formaldehyde dehydrogenase (FDH) enzyme-coupled demethylase activity assay
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additional information
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the bifunctional enzyme is active on H3K9me3/me2 and H3K36me3/me2 substrates. The cellular activity of recombinant KDM4A against its primary substrate, H3K9me3, displays a graded response to depleting oxygen concentrations in line with the data obtained using isolated protein
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additional information
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the bifunctional enzyme specifically demethylates Lys9 and Lys36 residues of histone H3 (EC 1.14.11.66)
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additional information
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the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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additional information
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the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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additional information
?
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the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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additional information
?
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the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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additional information
?
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the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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additional information
?
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the bifunctional enzyme is active on H3K9me3/me2 (EC 1.14.11.66) and H3K36me3/me2 substrates
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additional information
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general function of histone demethylase for histone 3 L-lysine 36 is to promote transcription elongation by antagonizing repressive L-lysine 36 methylation by Set2 methyltransferase
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additional information
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Rph1 is a histone demethylase that can specifically demethylate tri- and dimethylated Lys36 of histone H3. 2-Oxoglutarate forms hydrogen-bonding interactions with the side chains of conserved residues. The substrate-binding cleft of Rph1 is formed with several structural elements of the JmjC domain, the long beta-hairpin and the mixed structural motif, and the methylated Lys36 of H3 is recognized by several conserved residues of the JmjC domain. Molecular basis for the substrate specificity of Rph1, overview
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additional information
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Rph1 is a histone demethylase specific to tri-methylated-H3K36. Rph1 binds to the URS of PHR1 through ZF domains and modulates chromatin modifications in specific regions of the PHR1 promoter
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additional information
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Rph1 is a histone demethylase specific to tri-methylated-H3K36. Rph1 binds to the URS of PHR1 through ZF domains and modulates chromatin modifications in specific regions of the PHR1 promoter
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Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
a [histone H3]-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
a [histone H3]-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
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dimethyl-histone 3 L-lysine 36 + 2-oxoglutarate + O2
methyl-histone 3 L-lysine 36 + succinate + formaldehyde + CO2
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enzyme Rph1 is specific for di- and trimethyl-histone 3 L-lysine36
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histone H3 N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
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histone H3 N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
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histone H3 N6-methyl-L-lysine36 + 2-oxoglutarate + O2
histone H3 L-lysine36 + succinate + formaldehyde + CO2
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histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
trimethyl-histone 3 L-lysine 36 + 2-oxoglutarate + O2
dimethyl-histone 3 L-lysine 36 + succinate + formaldehyde + CO2
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enzyme Rph1 is specific for di- and trimethyl-histone 3 L-lysine36
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 26 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 26 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
[histone H3]-N6,N6,N6-trimethyllysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-N6-methyllysine36 + 2 succinate + 2 formaldehyde + 2 CO2
[histone H3]-N6,N6,N6-trimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyllysine36 + succinate + formaldehyde + CO2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
[histone H3]-N6,N6-dimethyl-L-lysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine36 + 2 succinate + 2 formaldehyde + 2 CO2
[histone H3]-N6,N6-dimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6-methyllysine36 + succinate + formaldehyde + CO2
additional information
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histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
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histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
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KDM4A demethylates H3K36me3, a modification enriched in the 3' end of active genes
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histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
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histone H3-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2
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histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
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histone H3-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2
histone H3-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyllysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-N6-methyllysine36 + 2 succinate + 2 formaldehyde + 2 CO2
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[histone H3]-N6,N6,N6-trimethyllysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-N6-methyllysine36 + 2 succinate + 2 formaldehyde + 2 CO2
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[histone H3]-N6,N6,N6-trimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyllysine36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6,N6-trimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyllysine36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6-dimethyl-L-lysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine36 + 2 succinate + 2 formaldehyde + 2 CO2
histone H3K36 methylation is enriched in coding regions of actively transcribed genes. dKDM4A is a JmjC domain-containing protein specifically demethylates H3K36me2 and H3K36me3 both in vitro and in vivo. H3K36 methylation is also subject to dynamic regulation. HP1a regulates histone H3K36 methylation in Drosophila larvae
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[histone H3]-N6,N6-dimethyl-L-lysine36 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine36 + 2 succinate + 2 formaldehyde + 2 CO2
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JmjC domain-containing protein dKDM4A is a histone H3K36 demethylase. Histone H3 methylation is one of the consistent marks distinguishing alternative chromatin packaging states
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[histone H3]-N6,N6-dimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6-methyllysine36 + succinate + formaldehyde + CO2
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[histone H3]-N6,N6-dimethyllysine36 + 2-oxoglutarate + O2
[histone H3]-N6-methyllysine36 + succinate + formaldehyde + CO2
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additional information
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HP1a and dKDM4A interact with each other and loss of HP1a leads to an increased level of histone H3K36me3
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additional information
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HP1a and dKDM4A interact with each other and loss of HP1a leads to an increased level of histone H3K36me3
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additional information
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JmjD2A is specific for H3K9me3 and H3K36me3 substrates. JmjD2A directly binds to regulatory regions of neural crest specifier genes in vivo
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additional information
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JMJD2A demethylates trimethylated histone K9/K36 to di- but not mono- or unmethylated products, i.e. JMJD2A also catalyzes the reactions of EC 1.14.11.66, H3K9 trimethyl demethylase
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additional information
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general function of histone demethylase for histone 3 L-lysine 36 is to promote transcription elongation by antagonizing repressive L-lysine 36 methylation by Set2 methyltransferase
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additional information
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Rph1 is a histone demethylase that can specifically demethylate tri- and dimethylated Lys36 of histone H3. 2-Oxoglutarate forms hydrogen-bonding interactions with the side chains of conserved residues. The substrate-binding cleft of Rph1 is formed with several structural elements of the JmjC domain, the long beta-hairpin and the mixed structural motif, and the methylated Lys36 of H3 is recognized by several conserved residues of the JmjC domain. Molecular basis for the substrate specificity of Rph1, overview
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additional information
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Rph1 is a histone demethylase specific to tri-methylated-H3K36. Rph1 binds to the URS of PHR1 through ZF domains and modulates chromatin modifications in specific regions of the PHR1 promoter
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additional information
?
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Rph1 is a histone demethylase specific to tri-methylated-H3K36. Rph1 binds to the URS of PHR1 through ZF domains and modulates chromatin modifications in specific regions of the PHR1 promoter
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Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
2-(2-((chroman-6-ylmethyl)amino)pyrimidin-4-yl)isonicotinic acid
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3-(9-(dimethylamino)-N-hydroxynonanamido)propanoic acid
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3-[hydroxy-[5-[[(1R)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-5-oxo-pentanoyl]amino]propanoic acid
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3-[hydroxy-[5-[[(1S)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-5-oxo-pentanoyl]amino]propanoic acid
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3-[hydroxy-[7-[[(1S)-2-methoxy-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-7-oxo-heptanoyl]amino]propanoic acid
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3-[hydroxy-[8-[[(1R)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-8-oxo-octanoyl]amino]propanoic acid
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3-[hydroxy-[8-[[(1S)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-8-oxo-octanoyl]amino]propanoic acid
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3-[hydroxy-[8-[[(1S)-2-methoxy-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-8-oxo-octanoyl]amino]propanoic acid
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5-tetrazolyl acetohydrazide
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8-(4-(2-(4-(3,5-dichlorophenyl)piperidin-1-yl)ethyl)-1H-pyrazol-1-yl)pyrido[3,4-d]pyrimidin-4(3H)-one
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8-(hydroxyamino)-N-[(1S)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]-8-oxo-octanamide
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Co2+
has an activating on multiple histone modifications at the global level. Cobalt ions significantly increase global histone H3K4me3, H3K9me2, H3K9me3, H3K27me3 and H3K36me3, as well as uH2A and uH2B and decreases acetylation at histone H4 (AcH4) in vivo. Cobalt ions increase H3K9me3 and H3K36me3 by inhibiting histone demethylation process in vivo. And cobalt ions directly inhibit demethylase activity of JMJD2A in vitro. Cobalt ions do not increase the level of uH2A in the in vitro histone ubiquitinating assay and inhibit histone-deubiquitinating enzyme activity in vitro
H2O2
loss of KDM4A activity in hypoxia resulting in changes to global histone lysine methylation
methyl (2S)-2-[[4-[3-(hydroxyamino)-3-oxo-propyl]benzoyl]amino]-3-(4-phenylphenyl)propanoate
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methyl (2S)-2-[[7-(hydroxyamino)-7-oxo-heptanoyl]amino]-3-(4-phenylphenyl)propanoate
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methyl (2S)-2-[[7-[hydroxy-(3-methoxy-3-oxo-propyl)amino]-7-oxo-heptanoyl]amino]-3-(4-phenylphenyl)propanoate
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methyl (2S)-2-[[8-[hydroxy-(3-methoxy-3-oxo-propyl)amino]-8-oxo-octanoyl]amino]-3-(4-phenylphenyl)propanoate
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methyl (S)-3-(2'-chloro-6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
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methyl (S)-3-(3'-cyano-6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
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methyl (S)-3-(3'-fluoro-6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
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methyl (S)-3-(4'-chloro-6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
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methyl (S)-3-(4'-cyano-6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
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methyl (S)-3-(4'-fluoro-6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
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methyl (S)-3-(6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
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methyl (S)-3-([1,1'-biphenyl]-4-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
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methyl 3-(3'-chloro-6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
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methyl 3-[hydroxy-[8-[[(1S)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-8-oxo-octanoyl]amino]propanoate
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N-[(1S)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]heptanamide
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N1-((3'-chloro-6-methoxy-[1,1'-biphenyl]-3-yl)methyl)-N8-hydroxyoctanediamide
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N1-(2-(3'-chloro-6-hydroxy-[1,1'-biphenyl]-3-yl)ethyl)-N8-hydroxyoctanediamide
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N1-(2-(3'-chloro-6-methoxy-[1,1'-biphenyl]-3-yl)ethyl)-N8-hydroxyoctanediamide
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SW55
a hydroxamate-based histone deacetylase (HDAC) inhibitor, slight inhibition
tert-butyl (2S)-2-[[8-(hydroxyamino)-8-oxo-octanoyl]amino]-3-(4-phenylphenyl)propanoate
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tert-butyl (2S)-2-[[8-(hydroxyamino)-8-oxo-octanoyl]amino]-3-phenyl-propanoate
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N-oxalylglycine
NOG, a nonreactive 2-OG analogue
Ni2+
substitutes for Fe(II) and inhibits the hydroxylation reaction
additional information
4-biphenylalanine- and 3-phenyltyrosine-derived hydroxamic acids are inhibitors of the JumonjiC-domain-containing histone demethylase KDM4A, synthesis and chemical modifications on the lead structure and biochemical evaluation, structure-activity relationships, overview. For KDM4A inhibition, the best compounds are those bearing a biphenylalanine cap (both configurations) with an additional hydroxamic acid moiety, a C8 alkyl chain as spacer, and an N-alkylated warhead for the selectivity against hydroxamate-based histone deacetylases, HDACs, methyl 3-[hydroxy-[8-[[(1S)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-8-oxo-octanoyl]amino]propanoate and 3-[hydroxy-[8-[[(1R)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-8-oxo-octanoyl]amino]propanoic acid. Effect of inhibitors compounds methyl (2S)-2-[[7-[hydroxy-(3-methoxy-3-oxo-propyl)amino]-7-oxo-heptanoyl]amino]-3-(4-phenylphenyl)propanoate, 3-[hydroxy-[7-[[(1S)-2-methoxy-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-7-oxo-heptanoyl]amino]propanoic acid, methyl (2S)-2-[[8-[hydroxy-(3-methoxy-3-oxo-propyl)amino]-8-oxo-octanoyl]amino]-3-(4-phenylphenyl)propanoate, and 3-[hydroxy-[8-[[(1S)-2-methoxy-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-8-oxo-octanoyl]amino]propanoic acid on on cell proliferation of KYSE-150 and HL-60 cells. Cell-permeable derivatives clearly show a demethylase-inhibition-dependent antiproliferative effect against HL-60 human promyelocytic leukemia cells
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additional information
structures of JMJD2A-Ni(II)-Zn(II) inhibitor complexes bound to tri-, di- and monomethyl forms of H3K9 and the trimethyl form of H3K36, overview
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additional information
-
expression of GTT1, UGX2, CTT1, and HSP26 is highly induced by H2O2 treatment and causes the dissociation of Rph1 from the promoters of these genes
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0.037
2-(2-((chroman-6-ylmethyl)amino)pyrimidin-4-yl)isonicotinic acid
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.003
3-(9-(dimethylamino)-N-hydroxynonanamido)propanoic acid
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.2
3-[hydroxy-[5-[[(1R)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-5-oxo-pentanoyl]amino]propanoic acid
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0703
3-[hydroxy-[5-[[(1S)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-5-oxo-pentanoyl]amino]propanoic acid
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0606
3-[hydroxy-[7-[[(1S)-2-methoxy-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-7-oxo-heptanoyl]amino]propanoic acid
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0068
3-[hydroxy-[8-[[(1R)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-8-oxo-octanoyl]amino]propanoic acid
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0136
3-[hydroxy-[8-[[(1S)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-8-oxo-octanoyl]amino]propanoic acid
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0371
3-[hydroxy-[8-[[(1S)-2-methoxy-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-8-oxo-octanoyl]amino]propanoic acid
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0466
5-tetrazolyl acetohydrazide
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0085
8-(hydroxyamino)-N-[(1S)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]-8-oxo-octanamide
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0258
methyl (2S)-2-[[4-[3-(hydroxyamino)-3-oxo-propyl]benzoyl]amino]-3-(4-phenylphenyl)propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0706
methyl (2S)-2-[[7-(hydroxyamino)-7-oxo-heptanoyl]amino]-3-(4-phenylphenyl)propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.056
methyl (2S)-2-[[7-[hydroxy-(3-methoxy-3-oxo-propyl)amino]-7-oxo-heptanoyl]amino]-3-(4-phenylphenyl)propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0171
methyl (2S)-2-[[8-[hydroxy-(3-methoxy-3-oxo-propyl)amino]-8-oxo-octanoyl]amino]-3-(4-phenylphenyl)propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0563
methyl (S)-3-(2'-chloro-6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0476
methyl (S)-3-(3'-cyano-6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.029
methyl (S)-3-(3'-fluoro-6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0483
methyl (S)-3-(4'-chloro-6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0548
methyl (S)-3-(4'-cyano-6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0522
methyl (S)-3-(4'-fluoro-6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0939
methyl (S)-3-(6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0254
methyl (S)-3-([1,1'-biphenyl]-4-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0276
methyl 3-(3'-chloro-6-hydroxy-[1,1'-biphenyl]-3-yl)-2-(8-(hydroxyamino)-8-oxooctanamido)propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0068
methyl 3-[hydroxy-[8-[[(1S)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]amino]-8-oxo-octanoyl]amino]propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.2
N-[(1S)-2-(hydroxyamino)-2-oxo-1-[(4-phenylphenyl)methyl]ethyl]heptanamide
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0145
N1-((3'-chloro-6-methoxy-[1,1'-biphenyl]-3-yl)methyl)-N8-hydroxyoctanediamide
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0188
N1-(2-(3'-chloro-6-hydroxy-[1,1'-biphenyl]-3-yl)ethyl)-N8-hydroxyoctanediamide
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0166
N1-(2-(3'-chloro-6-methoxy-[1,1'-biphenyl]-3-yl)ethyl)-N8-hydroxyoctanediamide
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0254
SW55
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.0143
tert-butyl (2S)-2-[[8-(hydroxyamino)-8-oxo-octanoyl]amino]-3-(4-phenylphenyl)propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
0.201
tert-butyl (2S)-2-[[8-(hydroxyamino)-8-oxo-octanoyl]amino]-3-phenyl-propanoate
Homo sapiens
pH 7.5, 37°C, recombinant enzyme
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evolution
KDM4A belongs to the KDM4 family
evolution
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Rph1 is a histone demethylase containing a Jumonji C (JmjC) domain and belongs to the C2H2 zinc-finger protein family
evolution
the enzyme belongs to the Jmjd2 family of H3K9/H3K36 histone demethylases
evolution
the enzyme belongs to the KDM2-8 family, KDM4 (also known as JMJD2) subfamily, which divided into five isoforms A-E
evolution
enzyme CG15835 shows higher identity to mammalian JMJD2D (40%) than to any of the other mammalian JMJD2 isoforms (22%)
evolution
enzyme CG33182 shows higher identity to mammalian JMJD2D (40%) than to any of the other mammalian JMJD2 isoforms (22%)
evolution
JMJD2A is a JmjC histone demethylase (HDM)
evolution
the Drosophila melanogaster HDM gene Dmel\Kdm4A is a homologue of the human JMJD2 family. Dmel\JHMD1, Dmel\JHMD2, and Dmel\Kdm4A are each highly conserved with their human homologue counterparts
evolution
the enzyme belongs to the KDM4/JmjC demethylase histone demethylase family. The selectivity of KDM4 enzymes is determined by multiple interactions within the catalytic domain but outside the active site. All KDM4 subfamily members have highly conserved residues lining the methylammonium-binding pocket. The exceptions are Ser288A/Ser-289B/Ser290C and Thr289A/Thr290B/Thr291C in KDM4A, B, and C, which are substituted by Ala287D/Ala289E/Ala286F and Ile288D/Ile290E/Ile287F in KDM4D-F, respectively. Evolutionary analysis of the KDM4 demethylase subfamily
evolution
the enzyme belongs to the KDM4/JmjC demethylase histone demethylase family. The selectivity of KDM4 enzymes is determined by multiple interactions within the catalytic domain but outside the active site. Evolutionary analysis of the KDM4 demethylase subfamily
evolution
the enzyme encoded by gene AN1060 (designated as kdmA) is a member of the mammalian KDM4 family of proteins (also known as JHDM3/JMJD2 in mammals)
evolution
the human KDM4 family consists of four members, KDM4A-D (also known as JMJD2A-D). These enzymes specifically catalyze the demethylation of H3K9me3/me2, H3K36me2/me3 and H1.4K26me2/me3 in a Fe2+ and 2-oxoglutarate-dependent manner. Besides the catalytic JmjC domain, KDM4 demethylases contain the JmjN domain, which is also required for the demethylase activity. In addition, all KDM4 members, except the shortest KDM4D protein, contain two Plant homeodomain (PHD) and two Tudor domains. Gene KDM4D is Y chromosome-encoded and a truncated enzyme variant compared to KDM4A-C
evolution
the human KDM4 family consists of four members, KDM4A-D (also known as JMJD2A-D). These enzymes specifically catalyze the demethylation of H3K9me3/me2, H3K36me2/me3 and H1.4K26me2/me3 in a Fe2+ and 2-oxoglutarate-dependent manner. Besides the catalytic JmjC domain, KDM4 demethylases contain the JmjN domain, which is also required for the demethylase activity. In addition, all KDM4 members, except the shortest KDM4D protein, contain two Plant homeodomain (PHD) and two Tudor domains. PHD and Tudor domains are not required for KDM4 enzymatic activity. Gene KDM4D is Y chromosome-encoded and a truncated enzyme variant compared to KDM4A-C
evolution
-
Rph1 is a histone demethylase containing a Jumonji C (JmjC) domain and belongs to the C2H2 zinc-finger protein family
-
evolution
-
the enzyme belongs to the Jmjd2 family of H3K9/H3K36 histone demethylases
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malfunction
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enzyme mutants show 99 misregulated genes in first instar larvae. dKDM4A overexpression results in a global decrease in H3K36me3 levels and male lethality, which might be caused by impaired dosage compensation
malfunction
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histone H3K36A mutant shows increased UV sensitivity. Deletion of rph1 leads to approximately 2fold enhancement of PHR1 under normal conditions. Overexpression of Rph1 reduces the expression of PHR1 and increased UV sensitivity. The catalytically deficient mutant H235A of Rph1 diminishes the repressive transcriptional effect on PHR1 expression, which indicates that histone demethylase activity contributes to transcriptional repression
malfunction
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more than 75% of Rph1-regulated genes show increased expression in the rph1-deletion mutant
malfunction
changes in RENT component recruitment at NTS regions due to loss of H3 methylases or demethylases
malfunction
dysregulated expression of KDM4A-D family promotes chromosomal instabilities
malfunction
disruption of Dmel\Kdm4A results in a reduction of the male life span and a male-specific wing extension/twitching phenotype that occurs in response to other males and is reminiscent of an inter-male courtship phenotype involving the courtship song, phenotypes overview. Certain genes associated with each of these phenotypes are significantly downregulated in response to Dmel\Kdm4A loss, most notably the longevity associated Hsp22 gene and the male sex-determination fruitless gene
malfunction
dysregulated expression of KDM4A-D family promotes chromosomal instabilities. Dysregulation of KDM4C expression promotes mitotic chromosome missegregation. KDM4B-C members are overexpressed in several types of human cancer and its depletion impairs cancer cell proliferation
malfunction
dysregulated expression of KDM4A-D family promotes chromosomal instabilities. KDM4B-C members are overexpressed in several types of human cancer and its depletion impairs cancer cell proliferation
malfunction
KDM4A/JMJD2A overexpression leads to localized copy gain of 1q12, 1q21, and Xq13.1 without global chromosome instability, KDM4A-amplified tumors have increased copy gains for these same regions. 1q12h copy gain occurs within a single cell cycle, requires S phase, and is not stable but is regenerated each cell division. Sites with increased copy number are rereplicated and have increased KDM4A, MCM, and DNA polymerase occupancy. Suv39h1/KMT1A or HP1gamma overexpression suppresses the copy gain, whereas H3K9/K36 methylation interference promotes gain. Overexpression of a chromatin modifier results in site-specific copy gains
malfunction
knocking down JMJD2B expression by siRNA in gastric and other cancer cells inhibits cell proliferation and/or induces apoptosis and elevates the expression of p53 and p21CIP1 proteins, mechanism of JMJD2B inhibition, overview. The enhanced p53 expression results from activation of the DNA damage response pathway
malfunction
lack of either Jmjd2a or Jmjd2b is compatible with embryonic stem cell self-renewal and embryonic development. Only specific genomic elements are affected upon loss of Jmjd2 function
malfunction
lack of either Jmjd2a or Jmjd2b is compatible with embryonic stem cell self-renewal and embryonic development. While individual Jmjd2 family members are dispensable for embryonic stem cell maintenance and embryogenesis, combined deficiency for specifically Jmjd2a and Jmjd2c leads to early embryonic lethality and impaired embryonic stem cell (ESC) self-renewal, with spontaneous differentiation towards primitive endoderm under permissive culture conditions, phenotype, overview. Only specific genomic elements are affected upon loss of Jmjd2 function. Loss of Jmjd2a and Jmjd2c has a drastic effect on ESC proliferation
malfunction
loss of JmjD2A function causes dramatic downregulation of neural crest specifier genes analyzed by multiplex NanoString and in situ hybridization. Cells overexpressing JmjD2A completely lack either H3K9me3 or H3K36me3 marks. Overexpression of JmjD2A in chicken fibroblasts specifically depletes H3K9me3 and H3K36me3. JmjD2A loss of function depletes Sox10 expression and expression of neural crest specifier genes Sox9, FoxD3, and Snail2, but not dorsal neural tube markers. JmjD2A knockdown inhibits demethylation of H3K9me3 on the Sox10 promoter
malfunction
mutations of the residues comprising the methylammonium-binding pocket abrogate demethylation by JMJD2A, with the exception of an S288A substitution, which augments activity, particularly toward H3K9me2
malfunction
overexpression of CG15835 results in spreading of HP1 into euchromatin and a strong decrease on the levels of H3K9me3 and H3K36me3, while the levels of H3K4me3 and H3K27me3 are not significantly altered. Demethylase activity of dJMJD2(1)/CG15835 depends on the JmjC domain, as it is abolished by mutations that affect its catalytic activity. The single-point mutation H195A, mutating one of the Fe2+ binding residues, abolishes demethylase activity of dJMJD2(1)/CG15835
malfunction
overexpression of the histone lysine demethylase KDM4A is related to the pathology of several human cancers
malfunction
Pim1 knockdown and P21(WAF1/Cip1) overexpression fully abrogates the oncogenic function of JMJD2A. A 39KD JMJD2A transcript, JMJD2ADELTA, is significantly increased in JMJD2A or miR372 overexpressing Hep3B cell line
malfunction
the kdmA mutant shows a significant increase in H3K36me3 during primary metabolism at the aflR and ipnA locus and some slightly higher levels at the aptA genes, the mutant has reduced levels of sterigmatocystin compared to wild-type. Manipulation of kdmA expression reveals genetic and environmental interactions including lethality under light. Deletion of kdmA causes light lethality and sensitivity to oxidative stress during vegetative growth to chronic oxidative stress
malfunction
-
histone H3K36A mutant shows increased UV sensitivity. Deletion of rph1 leads to approximately 2fold enhancement of PHR1 under normal conditions. Overexpression of Rph1 reduces the expression of PHR1 and increased UV sensitivity. The catalytically deficient mutant H235A of Rph1 diminishes the repressive transcriptional effect on PHR1 expression, which indicates that histone demethylase activity contributes to transcriptional repression
-
malfunction
-
more than 75% of Rph1-regulated genes show increased expression in the rph1-deletion mutant
-
malfunction
-
the kdmA mutant shows a significant increase in H3K36me3 during primary metabolism at the aflR and ipnA locus and some slightly higher levels at the aptA genes, the mutant has reduced levels of sterigmatocystin compared to wild-type. Manipulation of kdmA expression reveals genetic and environmental interactions including lethality under light. Deletion of kdmA causes light lethality and sensitivity to oxidative stress during vegetative growth to chronic oxidative stress
-
malfunction
-
the kdmA mutant shows a significant increase in H3K36me3 during primary metabolism at the aflR and ipnA locus and some slightly higher levels at the aptA genes, the mutant has reduced levels of sterigmatocystin compared to wild-type. Manipulation of kdmA expression reveals genetic and environmental interactions including lethality under light. Deletion of kdmA causes light lethality and sensitivity to oxidative stress during vegetative growth to chronic oxidative stress
-
malfunction
-
the kdmA mutant shows a significant increase in H3K36me3 during primary metabolism at the aflR and ipnA locus and some slightly higher levels at the aptA genes, the mutant has reduced levels of sterigmatocystin compared to wild-type. Manipulation of kdmA expression reveals genetic and environmental interactions including lethality under light. Deletion of kdmA causes light lethality and sensitivity to oxidative stress during vegetative growth to chronic oxidative stress
-
malfunction
-
lack of either Jmjd2a or Jmjd2b is compatible with embryonic stem cell self-renewal and embryonic development. While individual Jmjd2 family members are dispensable for embryonic stem cell maintenance and embryogenesis, combined deficiency for specifically Jmjd2a and Jmjd2c leads to early embryonic lethality and impaired embryonic stem cell (ESC) self-renewal, with spontaneous differentiation towards primitive endoderm under permissive culture conditions, phenotype, overview. Only specific genomic elements are affected upon loss of Jmjd2 function. Loss of Jmjd2a and Jmjd2c has a drastic effect on ESC proliferation
-
malfunction
-
lack of either Jmjd2a or Jmjd2b is compatible with embryonic stem cell self-renewal and embryonic development. Only specific genomic elements are affected upon loss of Jmjd2 function
-
malfunction
-
the kdmA mutant shows a significant increase in H3K36me3 during primary metabolism at the aflR and ipnA locus and some slightly higher levels at the aptA genes, the mutant has reduced levels of sterigmatocystin compared to wild-type. Manipulation of kdmA expression reveals genetic and environmental interactions including lethality under light. Deletion of kdmA causes light lethality and sensitivity to oxidative stress during vegetative growth to chronic oxidative stress
-
malfunction
-
the kdmA mutant shows a significant increase in H3K36me3 during primary metabolism at the aflR and ipnA locus and some slightly higher levels at the aptA genes, the mutant has reduced levels of sterigmatocystin compared to wild-type. Manipulation of kdmA expression reveals genetic and environmental interactions including lethality under light. Deletion of kdmA causes light lethality and sensitivity to oxidative stress during vegetative growth to chronic oxidative stress
-
metabolism
different roles of histone H3 methylases in regulating Net1/Sir2 recruitment to rDNA regions and the resultant rDNA silencing. In particular, both H3K4 and H3K79 methylation by Set1 and Dot1 positively regulate rDNA silencing, whereas H3K36 methylation by Set2 has the opposite effect
metabolism
exposure to Co2+ increases gene repression markers (H3K9me3, H3K27me3, H3K36me3, H3K9me2, uH2A and lack of AcH4), as well as gene activation markers (H3K4me3 and uH2B) in both A549 and Beas-2B cells. Cobalt ions increase H3K9me3 and H3K36me3 by inhibiting histone demethylation process in vivo
metabolism
KDM4A possesses the potential to act as an oxygen sensor in the context of epigenetic regulation
metabolism
many JmjC HDMs appear to function in the context of large multimeric complexes that govern their localization, transcriptional functions, and potentially their substrate specificity. In the case of certain JmjC enzymes, these complexes appear to be critical in conferring specificity for nucleosomal substrates
metabolism
the FBXO22-containing SCF E3 ubiquitin ligase complex controls the activity of KDM4A by targeting it for proteasomal turnover in a ubiquitin K48-dependent manner. FBXO22 functions as a receptor for KDM4A by recognizing its catalytic JmjN/JmjC domains via its intracellular signal transduction domain. Modulation of FBXO22 levels leads to increased or decreased levels of KDM4A, respectively. Changes in KDM4A abundance correlate with alterations in histone H3 lysine 9 and 36 methylation levels, and transcription of a KDM4A target gene, ASCL2
physiological function
c-Rph1, the catalytic core of Rph1, is responsible for the demethylase activity, which is essential for the transcription elongation of some actively transcribed genes
physiological function
-
dKDM4A demethylase activity regulates eu- and heterochromatic genes
physiological function
histone demethylase JMJD2B regulates chromatin structure or gene expression by removing methyl residues from trimethylated lysine 9 on histone H3 and is required for tumor cell proliferation and survival in vitro and in vivo, and is overexpressed in gastric cancer
physiological function
-
histone H3K36 demethylase Rph1/KDM4 regulates the expression of the photoreactivation gene PHR1, the demethylation at H3K36 is linked to UV sensitivity. Overexpression of Rph1 and H3K36A mutant reduced histone acetylation at the URS, which implies a crosstalk between histone demethylation and acetylation at the PHR1 promoter. Rph1 is a repressor of the DNA repair gene PHR1. Rph1 is dissociated from the PHR1 promoter in response to DNA damage. Rad53 regulates the expression of PHR1 and dissociation of Rph1 in response to DNA damage. Activated Rad53 complex phosphorylates Rph1 and S652A-mutated Rph1 impairs the dissociation in response to DNA damage
physiological function
-
identification of dKDM4A-regulated genes, overview. Appropriate expression levels for some dKDM4A-regulated genes rely on the demethylase activity of dKDM4A, whereas others do not. Highly expressed, many demethylase-dependent and independent genes are devoid of H3K36me3 in wild-type as well as in dKDM4A mutant larvae. Some of the most strongly affected genes in dKDM4A mutant animals are not regulated by H3K36 methylation
physiological function
-
Rph1 might be a regulatory node connecting different signaling pathways responding to environmental stresses. Rph1 is mainly a transcriptional repressor. Rph1-regulated genes respond to DNA damage and environmental stress. Microarray analysis, overview
physiological function
changes in histone H3 lysine methylation levels distinctly regulate rDNA silencing by recruiting different silencing proteins to rDNA, thereby contributing to rDNA silencing and nucleolar organization in yeast. The Rph1/Kdm4 demethylase is a JHDM3/JMJD2 orthologue and has in vivo demethylase activity toward H3K36me3/2. Enzyme Rph1 positively affects transcription
physiological function
Rph1 and Gis1 are reported to regulate the expression of PHR1, a photolyase gene required for the light-dependent repair of pyrimidine dimers. Both demethylases contain two zinc fingers and are damage responsive repressors of PHR1. Rph1 positively affects transcription
physiological function
-
anticancer agent nutlin kills MDM2-amplified cancer cells by altering histone methylation in an MDM2 proto-oncogene-dependent manner. MDM2 amplification increases histone methylation in nutlin-treated cells by causing depletion of histone demethylase JMJD2B. JMJD2B knockdown or inhibition increases H3K9/K36me3 levels, decreases ATG gene expression and autophagy, and sensitizes MDM2-nonamplified cells to apoptosis
physiological function
H3K36me3 acts as a barrier that prevents spreading of HP1 into euchromatin. Both H3K36 and H3K4 methylation associate to actively transcribed genes, suggesting that gene activity is a main determinant to delimit hetero- and euchromatic territories
physiological function
H3K36me3 acts as a barrier that prevents spreading of HP1 into euchromatin. Both H3K36 and H3K4 methylation associate to actively transcribed genes, suggesting that gene activity is a main determinant to delimit hetero- and euchromatic territories. dJMJD2(1)/CG15835 influences heterochromatin organization, but is excluded from heterochromatin. Overexpression of dJMJD2(1)/CG15835 does not affect the pattern of H3K9me2,3 at heterochromatin. dJMJD2(1)/CG15835 localizes to multiple euchromatic sites, where it mostly regulates H3K36me3, as its overexpression results in a strong decrease in the levels of H3K36me3. dJMJD2(1)/CG15835 regulates spreading of HP1
physiological function
H3K9me3 demethylase KDM4A/JMJD2A is able to increase accessibility and alter the replication timing at specific heterochromatic regions. KDM4A overexpression promotes copy gain of 1q12, 1q21, and Xq13.1 in cancer cells and results in site-specific copy gain of regions amplified in human tumors. These copy gains are not stably inherited but are generated transiently in each subsequent S phase and cleared by late G2. KDM4A is the only KDM4 family member that generated the gains in a catalytically dependent manner, copy gains are antagonized by coexpression of Suv39h1/KMT1A or HP1gamma, and promoted by H3K9 or H3K36 methylation interference. KDM4A associates with replication machinery and promotes rereplication of 1q12. KDM4A overexpression promotes chromatin state changes and recruitment of replication machinery. KDM4A-dependent 1q12h copy gain requires catalytic activity and Tudor domains, the KDM4A catalytic domain alone is insufficient to generate 1q12h gain
physiological function
histone demethylase Dmel\Kdm4A controls genes required for life span and male-specific sex determination in Drosophila melanogaster. Essential role for Dmel\Kdm4A in the transcriptional activation of genes involved in the aging process and male-specific neuronal formation and courtship behavior
physiological function
histone demethylases such as members of the Jumonji family revert histone trimethylation. Unlike other demethylases, JmjD2/KDM4 proteins have been shown to remove both lysine 9 and 36 trimethyl marks. Dynamic histone modifications are critical for proper temporal control of neural crest gene expression in vivo. The histone demethylase, JumonjiD2A (JmjD2A/KDM4A), is expressed in the forming neural folds. Direct stage-specific interactions of JmjD2A with regulatory regions of neural crest genes, associated temporal modifications in methylation states of lysine residues are directly affected by JmjD2A activity. Chromatin modifications directly control neural crest genes in vertebrate embryos via modulating histone methylation. JmjD2A plays an important role in neural crest development. H3K9me3 and H3K36me3 occupancy regulates neural crest specifier expression in vivo
physiological function
in mouse embryonic fibroblasts engineered for the inducible expression of KDM4B, upon inducing Kdm4b, H3K9/36me3 levels significantly decrease compared to non-induced controls, and H3K9me1 levels significantly increase, while H3K9me2 and H3K27me3 remain unchanged. Reduced H3K9/36me3 levels are restored after somatic nuclear transfer
physiological function
JMJD2A accelerates malignant progression of liver cancer cells in vitro and in vivo. Mechanistically, JMJD2A promotes the expression and mature of pre-miR372 epigenetically. Notably, miR372 blocks the editing of 13th exon-introns-14th exon and forms a novel transcript (JMJD2ADELTA) of JMJD2A. Enzyme JMJD2A is overexpressed in cancer and inhibits repair of DNA damage by reducing homologous recombination repair. Histone H3K36 trimethylation (H3K36me3) is associated with carcinogenesis. Histone H3 demethylase JMJD2A promotes growth of liver cancer cells, via Pim1-ppRB1-CDK2-CycinE-C-myc pathway, through upregulating miR372, JMJD2A enhances miR372 expression epigenetically, mechanism, overview. In particular, JMJD2A inhibits P21 (WAF1/Cip1) expression by decreasing H3K9me3 dependent on JMJD2ADELTA. JMJD2A enhances Pim1 transcription by suppressing P21(WAF1/Cip1) involving altered histone H3 lysine 9 methylation. Furthermore, through increasing the expression of Pim1, JMJD2A facilitates the interaction among pRB, CDK2 and CyclinE which prompts the transcription and translation of oncogenic C-myc. JMJD2A may trigger the demethylation of Pim1
physiological function
Jmjd2a and Jmjd2c both localize to H3K4me3-positive promoters, where they have widespread and redundant roles in preventing accumulation of H3K9me3 and H3K36me3. Jmjd2 catalytic activity is required for embryonic stem cell (ESC) maintenance. Jmjd2a and Jmjd2c are essential for early embryonic development. Recruitment of the Jmjd2 H3K9/H3K36 demethylases to H3K4me3-marked nucleosomes. Jmjd2a and Jmjd2c redundantly regulate histone methylation levels
physiological function
JMJD2A is implicated in transcriptional silencing and is associated with the retinoblastoma protein, class I HDACs, and the nuclear corepressor N-CoR. JMJD2A and its paralogue JMJD2D associate with the androgen receptor (AR) to upregulate the expression of AR-dependent genes. The transcriptional functions of JMJD2 enzymes appear to be context-dependent
physiological function
KDM4A overexpression promotes chromatin state changes and recruitment of replication machinery and leads to localized copy gain of cytogenetic bands 1q12, 1q21, and Xq13.1 without global chromosome instability. KDM4A-amplified tumors have increased copy gains for these same regions. 1q12h copy gain occurs within a single cell cycle, requires S phase and is not stable but regenerated each cell division. Sites with increased copy number are rereplicated and have increased KDM4A, MCM and DNA polymerase occupancy. Suv39h1/KMT1A or HP1gamma overexpression suppresses the copy gain, while H3K9/K36 methylation interference promotes gain
physiological function
KDM4A specifically demethylates H3K36me2 and me3 both in vitro and in vivo. Heterochromatin Protein 1a (HP1a) associates with KDMA4A. The chromoshadow domain of HP1a and a HP1-interacting motif of KDM4A are responsible for this interaction. HP1a stimulates the histone H3K36 demethylation activity of dKDM4A. Loss of HP1a leads to increased level of histone H3K36me3
physiological function
KdmA, a histone H3 demethylase with bipartite function, differentially regulates primary and secondary metabolism in Aspergillus nidulans. KdmA displays locus-specific histone H3 lysine demethylation activity
physiological function
levels of H3K4me modulate temperature sensitive alleles of the transcriptional elongation complex Spt6-Spn1. The Rpd3S histone deacetylase complex is the H3K4me effector underlying these Spt6-Spn1 genetic interactions. H3K4 and H3K36 demethylases JHD2 and RPH1 mediate this combinatorial control of Rpd3S histone deacetylase complex
physiological function
overexpression of JHDM3A abrogates recruitment of HP1 (heterochromatin protein 1) to heterochromatin. Knockdown of JHDM3A leads to increased levels of H3K9 methylation and upregulation of JHDM3A target gene ASCL2
physiological function
overexpression of JMJD2A reduces H3-K9/K36 trimethylation levels in cultured cells
physiological function
overexpression of Rph1 reduces the expression of photoreactivation gene PHR1 and increases UV sensitivity. Rph1 is associated at the upstream repression sequence of PHR1 through zinc-finger domains and is dissociated after UV irradiation. Overexpression of Rph1 and H3K36A mutant reduces histone acetylation at the URS. Protein Rad53 acts as an upstream regulator of Rph1 and dominates the phosphorylation of Rph1 that is required for efficient PHR1 expression and the dissociation of Rph1
physiological function
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papillomaviruses DNA is histone-associated in infected cells. Reducing H3K36me3 by overexpression of KDM4A blocks productive viral replication. H3K36me3 is enriched on the 3' end of the early region of the high-risk papillomavirus HPV31 genome in a SETD2-dependent manner
physiological function
reducing H3K36me3 levels by overexpressing KDM4A reduces homologous recombination repair events. Tumor suppressor SETD2 is also required for homologous recombination repair events
physiological function
RNAi depletion results in an increase in general trimethylation of H3-K9 and localizes H3-K36Me3 levels on meiotic chromosomes and triggers p53-dependent germline apoptosis
physiological function
Rph1 functions as a specific demethylase for H3 K36me3 and K36me2, directly regulating Lys36 methylation in transcribed regions. Both JmjC-domain proteins Jhd1 and Rph1 are required for normal levels of RNA polymerase II crosslinking to genes. Overexpression of either Jhd1 or Rph1 bypasses the requirement for the positive elongation factor gene BUR1
physiological function
Rph1 is mainly a transcriptional repressor, more than 75% of Rph1-regulated genes show increased expression in the Rph1-deletion mutant. The binding motif 5'-CCCCTWA-3' is overrepresented in the promoters of Rph1-repressed genes. A significant proportion of Rph1-regulated genes respond to DNA damage and environmental stress. Rph1 is a labile protein, and Rad53 negatively modulates Rph1 protein level. The JmjN domain is important in maintaining protein stability and the repressive effect of Rph1
physiological function
the histone lysine demethylase KDM4A regulates H3K9 and H3K36 methylation states
physiological function
the JmjC histone lysine demethylases (KDMs) are epigenetic regulators involved in the removal of methyl groups from post-translationally modified lysyl residues within histone tails, modulating gene transcription
physiological function
various types of human cancers exhibit amplification or deletion of KDM4A-D members, which selectively demethylate H3K9 and H3K36, thus implicating their activity in promoting carcinogenesis
physiological function
catalyzes the demethylation of di- and trimethylated Lys9 (reactions of EC 1.14.11.65 and 1.14.11.66) and Lys36 in histone H3 (reactions of EC 1.14.11.27 and 1.14.11.69). Jmjd2a responds to 5-hydroxytryptamine and promotes the expression of the brain-derived neurotrophic factor (Bdnf), a protein critically involved in neuropathic pain. JMJD2A binds to the promoter of Bdnf and demethylates H3K9me3 and H3K36me3 at the Bdnf promoter to promote the expression of Bdnf. JMJD2A promotes the expression of Bdnf during neuropathic pain and neuron-specific knockout of Jmjd2a blocks the hypersensitivity of mice undergoing chronic neuropathic pain
physiological function
depletion of KDM4A in prostate cancer cells inhibits their proliferation and survival in vivo and vitro. Deubiquitinase USP1 regulates KDM4A K48-linked deubiquitination and stability. c-Myc is a key downstream effector of the USP1-KDM4A/androgen receptor axis in driving prostate cancer cell proliferation. Upregulation of KDM4A expression with high USP1 expression is observed in most prostate tumors and inhibition of USP1 promotes prostate cancer cells response to therapeutic agent enzalutamide
physiological function
histone H3.3 G34R substitution mutation, found in paediatric gliomas, causes widespread changes in H3K9me3 and H3K36me3 level by interfering with the KDM4 family of K9/K36 demethylases. Expression of a targeted single-copy of H3.3 G34R at endogenous levels induces chromatin alterations that are comparable to a KDM4 isoforms A/B/C triple-knockout. H3.3 G34R preferentially binds KDM4 while simultaneously inhibiting its enzymatic activity
physiological function
JMJD2A displays higher expression in glioma tissues than that in normal brain tissues and lower levels of H3K9me3/H3K36me3 are found in glioma tissues. Knockdown of JMJD2A expression attenuates the growth and colony formation in glioma cell lines U251, T98G, and U87MG, whereas JMJD2A overexpression results in opposing effects. JMJD2A knockdown reduces the growth of glioma T98G cells in vivo. JMJD2A activates the Akt-mTOR pathway and promotes protein synthesis in glioma cells via promoting phosphoinositide-dependent kinase-1 expression
physiological function
KDM4 activity is required for hematopoietic stem cell (HSC) maintenance in vivo. The combined knockout of Kdm4a, Kdm4b, and Kdm4c leads to reduction of myeloid and lymphoid cells. In conditional KDM4A/B/C triple-knockout mice, the knockout leads to accumulation of H3K9me3 on transcription start sites and the corresponding downregulation of expression of several genes in HSCs. Genes Taf1b and Nom1, are essential for the maintenance of hematopoietic cells
physiological function
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histone H3K36 demethylase Rph1/KDM4 regulates the expression of the photoreactivation gene PHR1, the demethylation at H3K36 is linked to UV sensitivity. Overexpression of Rph1 and H3K36A mutant reduced histone acetylation at the URS, which implies a crosstalk between histone demethylation and acetylation at the PHR1 promoter. Rph1 is a repressor of the DNA repair gene PHR1. Rph1 is dissociated from the PHR1 promoter in response to DNA damage. Rad53 regulates the expression of PHR1 and dissociation of Rph1 in response to DNA damage. Activated Rad53 complex phosphorylates Rph1 and S652A-mutated Rph1 impairs the dissociation in response to DNA damage
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physiological function
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Rph1 might be a regulatory node connecting different signaling pathways responding to environmental stresses. Rph1 is mainly a transcriptional repressor. Rph1-regulated genes respond to DNA damage and environmental stress. Microarray analysis, overview
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physiological function
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KdmA, a histone H3 demethylase with bipartite function, differentially regulates primary and secondary metabolism in Aspergillus nidulans. KdmA displays locus-specific histone H3 lysine demethylation activity
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physiological function
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KdmA, a histone H3 demethylase with bipartite function, differentially regulates primary and secondary metabolism in Aspergillus nidulans. KdmA displays locus-specific histone H3 lysine demethylation activity
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physiological function
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KdmA, a histone H3 demethylase with bipartite function, differentially regulates primary and secondary metabolism in Aspergillus nidulans. KdmA displays locus-specific histone H3 lysine demethylation activity
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physiological function
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Jmjd2a and Jmjd2c both localize to H3K4me3-positive promoters, where they have widespread and redundant roles in preventing accumulation of H3K9me3 and H3K36me3. Jmjd2 catalytic activity is required for embryonic stem cell (ESC) maintenance. Jmjd2a and Jmjd2c are essential for early embryonic development. Recruitment of the Jmjd2 H3K9/H3K36 demethylases to H3K4me3-marked nucleosomes. Jmjd2a and Jmjd2c redundantly regulate histone methylation levels
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physiological function
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KdmA, a histone H3 demethylase with bipartite function, differentially regulates primary and secondary metabolism in Aspergillus nidulans. KdmA displays locus-specific histone H3 lysine demethylation activity
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physiological function
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KdmA, a histone H3 demethylase with bipartite function, differentially regulates primary and secondary metabolism in Aspergillus nidulans. KdmA displays locus-specific histone H3 lysine demethylation activity
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additional information
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a modest increase in global H3K36me3 levels is compatible with viability, fertility, and the expression of most genes, whereas decreased H3K36me3 levels are detrimental in males
additional information
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Rph1 is a labile protein, and Rad53 negatively modulates Rph1 protein level. The JmjN domain is important in maintaining protein stability and the repressive effect of Rph1. Binding motif 5'-CCCCTWA-3', which resembles the stress response element, is overrepresented in the promoters of Rph1-repressed genes. JmjN and ZF domains of Rph1 are required for its function. Rph1 binds to gene promoters and is dissociated with DNA damage
additional information
cellular demethylase activity of KDM4A demonstrates a graded response to oxygen concentration in U2OS cells. Analysis of the H3K27me3 (cf. EC 1.14.11.68) mark shows loss of this mark upon overexpression of KDM4A in normoxia, with a graded response to oxygen similar to that seen for H3K9me3, although less-pronounced. H3K27me3 is not a canonical substrate for KDM4A, hence, loss of this mark cannot be directly attributed to catalytic KDM4A activity. Effect of oxygen availability on the activity of the KDM4 subfamily member KDM4A, overview. A high level of O2 sensitivity both with isolated protein and in cells is observed
additional information
enzyme structure-function relationships and substrate selectivity, comparisons of KDM4 enzymes, overview
additional information
enzyme structure-function relationships and substrate selectivity, comparisons of KDM4 enzymes, overview
additional information
enzyme structure-function relationships and substrate selectivity, comparisons of KDM4 enzymes, overview
additional information
in H3K9me3- and H3K36me3-enzyme complexes, the peptides bind in the same directionality within the substrate binding cleft of JMJD2A, depositing the trimethyllysines into the active site. The majority of the interactions between the enzyme and H3 peptides involve hydrogen bond and van der Waals interactions with the backbone atoms in the substrates. The residues N-terminal to the trimethyllysines adopt a similar beta-strand-like conformation, while the C-terminal residues in the peptides adopt distinct binding modes. Mono-, di-, and trimethyllysines bind within a methylammonium binding pocket adjacent to the Fe(II) and 2-oxoglutarate binding sites in JMJD2A. This pocket is lined with an array of oxygen atoms that participate in direct contacts with zeta-methyl groups of the trimethylated substrate. Structure-activity analysis, overview
additional information
interaction between JMJD2A and substrate peptides largely involves the main chains of the enzyme and the peptide. The peptide-binding specificity is primarily determined by the primary structure of the peptide, which explains the specificity of JMJD2A for methylated H3K9 and H3K36 instead of other methylated residues such as H3K27. The specificity for a particular methyl group is affected by multiple factors, such as space and the electrostatic environment in the catalytic center of the enzyme. Mechanisms and specificity of histone demethylation, overview. Residues Q86, N88, D135, and Y175 are involved in the interaction with the peptide, whereas residues Y177, N290, S288, and T289 are involved in methyl group binding. K241 is proposed to recruit the O2 molecule into the catalytic center. Glycine residues at +3 or +4 in the substrate are essential for substrate specificity
additional information
residue S288 modulates the methylation-state specificities of JMJD2 enzymes and other trimethyllysine-specific JmjC HDMs. The mechanisms by which JMJD2A discriminates against the demethylation of H3K4me and H4K20me. An alignment of the H3K4, H3K9, H3K36 and H4K20 methylation sites reveals substantial sequence diversity among the methylation motifs. The methylammonium-binding pocket is composed of the carbonyl oxygen of Gly170, the hydroxyl groups of Tyr177 and Ser288, and the carboxylate side chain of Glu190. Active site site structure with bound substrate, overview
additional information
the mechanism for achieving methylation state selectivity involves the orientation of the substrate methyl groups towards a ferryl intermediate. Active site structure and mechanism of JMJD2A, overview
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V423A
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site-directed mutagenesis, the point mutation at the central valine of PxVxL motif disrupts the interaction between dKDM4A and HP1a in vitro
G133A
site-directed mutagenesis, the mutation in the catalytic domain abrogates enzyme activity
G138A
site-directed mutagenesis, the mutation in the catalytic domain abrogates enzyme activity
G165A
site-directed mutagenesis, the mutation in the catalytic domain abrogates enzyme activity
G170A
site-directed mutagenesis, the mutation in the catalytic domain abrogates enzyme activity
S288N
site-directed mutagenesis, the mutation in the catalytic domain abrogates enzyme activity
T289B
site-directed mutagenesis, the mutation in the catalytic domain abrogates enzyme activity
D191A
site-directed mutagenesis, the mutant shows about 95%reduced activity with H3K9me3 compared to wild-type, and no activity with H3K36me3
N290A
site-directed mutagenesis, the mutant shows no activity with H3K36me3 and almost no activity with H3K9me3
N290D
site-directed mutagenesis, the mutant shows about 98%reduced activity with H3K9me3 compared to wild-type, and no activity with H3K36me3
R919D
site-directed mutagenesis, the mutant is not associated with mitotic chromatin in contrast to the wild-type enzyme
S198M
site-directed mutagenesis, a KDM4C demethylase dead mutant
Y175F
site-directed mutagenesis, the mutant shows about 90%reduced activity with H3K9me3 compared to wild-type, and no activity with H3K36me3
Y177F
site-directed mutagenesis, the mutant shows about 90%reduced activity with H3K9me3 compared to wild-type, and no activity with H3K36me3
H195A
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site-directed mutagenesis
H195A
construction of a mutant dKDM4A in which a conserved amino acid in the iron-binding site is mutated to alanine, the mutant dKDM4A has no demethylation activity on histones H3K36me3 and H3K36me2
H195A
site-directed mutagenesis, mutation of an Fe2+ binding residue, abolishes demethylase activity of dJMJD2(1)/CG15835
S288A
mutation augments activity, particularly toward H3K9me2
S288A
mutations of the residues comprising the methylammonium-binding pocket abrogate demethylation by JMJD2A, with the exception of an S288A substitution, which augments activity, particularly toward H3K9me2
H235A
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catalytically deficient mutant
H235A
catalytically deficient mutant
H235A
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catalytically deficient mutant
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additional information
the kdmA mutant shows a significant increase in H3K36me3 during primary metabolism at the aflR and ipnA locus and some slightly higher levels at the aptA genes, the mutant has reduced levels of sterigmatocystin compared to wild-type, mutant phenotype, overview. Deletion of kdmA in Aspergillus nidulans produces both positive and negative changes in transcriptional readouts and the number of affected genes is different under different conditions. KdmA deletion alters expression pattern of secondary metabolism cluster genes in secondary metabolism phase, analysis of the heat map for mean expression of previously annotated secondary metabolism clusters. Deletion of kdmA causes light lethality and sensitivity to oxidative stress during vegetative growth
additional information
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the kdmA mutant shows a significant increase in H3K36me3 during primary metabolism at the aflR and ipnA locus and some slightly higher levels at the aptA genes, the mutant has reduced levels of sterigmatocystin compared to wild-type, mutant phenotype, overview. Deletion of kdmA in Aspergillus nidulans produces both positive and negative changes in transcriptional readouts and the number of affected genes is different under different conditions. KdmA deletion alters expression pattern of secondary metabolism cluster genes in secondary metabolism phase, analysis of the heat map for mean expression of previously annotated secondary metabolism clusters. Deletion of kdmA causes light lethality and sensitivity to oxidative stress during vegetative growth
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additional information
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the kdmA mutant shows a significant increase in H3K36me3 during primary metabolism at the aflR and ipnA locus and some slightly higher levels at the aptA genes, the mutant has reduced levels of sterigmatocystin compared to wild-type, mutant phenotype, overview. Deletion of kdmA in Aspergillus nidulans produces both positive and negative changes in transcriptional readouts and the number of affected genes is different under different conditions. KdmA deletion alters expression pattern of secondary metabolism cluster genes in secondary metabolism phase, analysis of the heat map for mean expression of previously annotated secondary metabolism clusters. Deletion of kdmA causes light lethality and sensitivity to oxidative stress during vegetative growth
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additional information
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the kdmA mutant shows a significant increase in H3K36me3 during primary metabolism at the aflR and ipnA locus and some slightly higher levels at the aptA genes, the mutant has reduced levels of sterigmatocystin compared to wild-type, mutant phenotype, overview. Deletion of kdmA in Aspergillus nidulans produces both positive and negative changes in transcriptional readouts and the number of affected genes is different under different conditions. KdmA deletion alters expression pattern of secondary metabolism cluster genes in secondary metabolism phase, analysis of the heat map for mean expression of previously annotated secondary metabolism clusters. Deletion of kdmA causes light lethality and sensitivity to oxidative stress during vegetative growth
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additional information
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the kdmA mutant shows a significant increase in H3K36me3 during primary metabolism at the aflR and ipnA locus and some slightly higher levels at the aptA genes, the mutant has reduced levels of sterigmatocystin compared to wild-type, mutant phenotype, overview. Deletion of kdmA in Aspergillus nidulans produces both positive and negative changes in transcriptional readouts and the number of affected genes is different under different conditions. KdmA deletion alters expression pattern of secondary metabolism cluster genes in secondary metabolism phase, analysis of the heat map for mean expression of previously annotated secondary metabolism clusters. Deletion of kdmA causes light lethality and sensitivity to oxidative stress during vegetative growth
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additional information
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the kdmA mutant shows a significant increase in H3K36me3 during primary metabolism at the aflR and ipnA locus and some slightly higher levels at the aptA genes, the mutant has reduced levels of sterigmatocystin compared to wild-type, mutant phenotype, overview. Deletion of kdmA in Aspergillus nidulans produces both positive and negative changes in transcriptional readouts and the number of affected genes is different under different conditions. KdmA deletion alters expression pattern of secondary metabolism cluster genes in secondary metabolism phase, analysis of the heat map for mean expression of previously annotated secondary metabolism clusters. Deletion of kdmA causes light lethality and sensitivity to oxidative stress during vegetative growth
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additional information
construction of a P-element insertion mutant of dKDMA4, the mutant is homozygous viable, the P element insertion elevates the bulk level of histone H3K36me3 in mutant embryos. Overexpression of dKDM4A seems to only lead to demethylation of histone H3K36, since the level of histone H3K9me3 and H3K4me2 remains unchanged
additional information
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construction of a P-element insertion mutant of dKDMA4, the mutant is homozygous viable, the P element insertion elevates the bulk level of histone H3K36me3 in mutant embryos. Overexpression of dKDM4A seems to only lead to demethylation of histone H3K36, since the level of histone H3K9me3 and H3K4me2 remains unchanged
additional information
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generation of dkdm4a mutant embryos, the dkdm4a allele contains a P-element inserted within the first exon of the gene and abrogates dKDM4A transcription
additional information
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generation of JmjC protein dKDM4A mutant allele, DELTAdKDM4A, with a deletion spanning from 47 nucleotides downstream of the ATG to the end of the gene by means of imprecise excision of the P-element P{GawB}NP0618
additional information
construction of transgenic lines carrying a UASGAL4-CG15835-Flag construct, where expression of dJMJD2(1)/CG15835 is under the control of the yeast activator GAL4, allowing its overexpression upon crossing with lines expressing GAL4. Overexpression of CG15835 results in spreading of HP1 into euchromatin and a strong decrease on the levels of H3K9me3 and H3K36me3
additional information
construction of transgenic lines carrying a UASGAL4-CG15835-Flag construct, where expression of dJMJD2(1)/CG15835 is under the control of the yeast activator GAL4, allowing its overexpression upon crossing with lines expressing GAL4. Overexpression of CG15835 results in spreading of HP1 into euchromatin and a strong decrease on the levels of H3K9me3 and H3K36me3
additional information
overexpression of JmjD2A in fibroblasts specifically depletes H3K9me3 and H3K36me3
additional information
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A, construction of diverse chimeric enzyme mutants, overview. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization
additional information
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A, construction of diverse chimeric enzyme mutants, overview. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization
additional information
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A, construction of diverse chimeric enzyme mutants, overview. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization
additional information
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A, construction of diverse chimeric enzyme mutants, overview. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization. EGFP-KDM4CRDTF/DNLY mutant is excluded from mitotic chromatin. For isozyme knockout, U2OS cells are transfected with KDM4B-C siRNA sequences
additional information
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A, construction of diverse chimeric enzyme mutants, overview. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization. EGFP-KDM4CRDTF/DNLY mutant is excluded from mitotic chromatin. For isozyme knockout, U2OS cells are transfected with KDM4B-C siRNA sequences
additional information
enzyme engineering and swapping of the C-terminus region containing the distal Tudor domain between isozymes KDM4C and KDM4A, construction of diverse chimeric enzyme mutants, overview. Chimera5, which encodes the first 934 amino acids of KDM4C fused with the last 129 amino acid containing the distal Tudor domain of KDM4A, is excluded from mitotic chromatin. On the other hand, chimera6 that encodes the first 954 amino acids of KDM4A fused to 101 amino acids of KDM4C, which includes its distal Tudor domain, remains excluded from chromatin. The C-terminus of KDM4C containing the distal Tudor domain is essential but not sufficient for its mitotic chromatin localization. EGFP-KDM4CRDTF/DNLY mutant is excluded from mitotic chromatin. For isozyme knockout, U2OS cells are transfected with KDM4B-C siRNA sequences
additional information
introduction of a di-glycine motif at the +3 to +4 positions of the H3K27 sequence, a site which shares sequence homology with the H3K9 sequence, enables JMJD2A to efficiently demethylate H3K27me3, cf. EC 1.14.11.68
additional information
JMJD2A knockout or overexpression in Hep-3B cells. Construction of JMJD2ADELTA mutant. A 39KD JMJD2A transcript, JMJD2ADELTA, is significantly increased in JMJD2A or miR372 overexpressing Hep3B cell line
additional information
Jmjd2b knockdown by siRNA, leading to induction of p53 via activation of the DNA damage response pathway. p53 Inhibition significantly restored the clonogenic potential of AGS and HeLa cells treated with JMJD2B siRNA. Increased apoptosis in BGC-823 and HeLa cells but not AGS cells with JMJD2B siRNA knockdown. AGS cells are arrested at the G1 phase, but BGC-823 and HeLa cells are arrested at the S phase
additional information
transposition of the Ala-Pro motif of H3K27 to AARK(me3)SPAAT, to mimic the proline position in H3K36, resulted in no detectable activity
additional information
generation of conditional Jmjd2a/Kdm4a, Jmjd2b/Kdm4b and Jmjd2c/Kdm4c/Gasc1 single, double and triple knockout mouse embryonic stem cells (ESCs). While individual Jmjd2 family members are dispensable for ESC maintenance and embryogenesis, combined deficiency for specifically Jmjd2a and Jmjd2c leads to early embryonic lethality and impaired ESC self-renewal, with spontaneous differentiation towards primitive endoderm under permissive culture conditions. Increased H3K9me3 levels in knockout ESCs compromise the expression of several Jmjd2a/c targets, including genes that are important for ESC self-renewal. Thus, continual removal of H3K9 promoter methylation by Jmjd2 demethylases represents a novel mechanism ensuring transcriptional competence and stability of the pluripotent cell identity. Phenotypes, overview
additional information
generation of conditional Jmjd2a/Kdm4a, Jmjd2b/Kdm4b and Jmjd2c/Kdm4c/Gasc1 single, double and triple knockout mouse embryonic stem cells (ESCs). While individual Jmjd2 family members are dispensable for ESC maintenance and embryogenesis, combined deficiency for specifically Jmjd2a and Jmjd2c leads to early embryonic lethality and impaired ESC self-renewal, with spontaneous differentiation towards primitive endoderm under permissive culture conditions. Increased H3K9me3 levels in knockout ESCs compromise the expression of several Jmjd2a/c targets, including genes that are important for ESC self-renewal. Thus, continual removal of H3K9 promoter methylation by Jmjd2 demethylases represents a novel mechanism ensuring transcriptional competence and stability of the pluripotent cell identity. Phenotypes, overview
additional information
generation of conditional Jmjd2a/Kdm4a, Jmjd2b/Kdm4b and Jmjd2c/Kdm4c/Gasc1 single, double and triple knockout mouse embryonic stem cells (ESCs). While individual Jmjd2 family members are dispensable for ESC maintenance and embryogenesis, combined deficiency for specifically Jmjd2a and Jmjd2c leads to early embryonic lethality and impaired ESC self-renewal, with spontaneous differentiation towards primitive endoderm under permissive culture conditions. Increased H3K9me3 levels in knockout ESCs compromise the expression of several Jmjd2a/c targets, including genes that are important for ESC self-renewal. Thus, continual removal of H3K9 promoter methylation by Jmjd2 demethylases represents a novel mechanism ensuring transcriptional competence and stability of the pluripotent cell identity. Phenotypes, overview
additional information
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generation of conditional Jmjd2a/Kdm4a, Jmjd2b/Kdm4b and Jmjd2c/Kdm4c/Gasc1 single, double and triple knockout mouse embryonic stem cells (ESCs). While individual Jmjd2 family members are dispensable for ESC maintenance and embryogenesis, combined deficiency for specifically Jmjd2a and Jmjd2c leads to early embryonic lethality and impaired ESC self-renewal, with spontaneous differentiation towards primitive endoderm under permissive culture conditions. Increased H3K9me3 levels in knockout ESCs compromise the expression of several Jmjd2a/c targets, including genes that are important for ESC self-renewal. Thus, continual removal of H3K9 promoter methylation by Jmjd2 demethylases represents a novel mechanism ensuring transcriptional competence and stability of the pluripotent cell identity. Phenotypes, overview
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additional information
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overexpression bypasses the requirement for the positive elongation factor gene BUR1
additional information
generation of a rph1DELTA deletion mutant, phenotype overview
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