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Information on EC 1.14.11.66 - [histone H3]-trimethyl-L-lysine9 demethylase and Organism(s) Mus musculus and UniProt Accession Q8BW72
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1.14.11.66 [histone H3]-trimethyl-L-lysine9 demethylaseIUBMB Comments
Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated Lys-9 residues in the tail of the histone protein H3 (H3K9). This lysine residue can exist in three methylation states (mono-, di- and trimethylated), but this group of enzymes only act on the the tri- and di-methylated forms. The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. cf. EC 1.14.11.65, [histone H3]-dimethyl-L-lysine9 demethylase.
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Word Map
- 1.14.11.66
- chromatin
-
demethylation
- demethylases
-
trimethylation
- metastasis
- tumorigenesis
- prostate
- leukemia
- methyltransferases
-
pluripotent
-
corepressors
- heterochromatin
- nucleosome
-
hypoxia-inducible
-
self-renewal
- mesenchymal
- tranylcypromine
-
polycomb
-
h3k4me2
- androgen
- myeloid
-
chromatin-modifying
-
histone-modifying
-
chip-seq
- lys4
- corest
-
flavin-dependent
- hdacs
-
monoamine
-
epigenome
- deacetylases
- medicine
- suv39h1
- analysis
-
chip-qpcr
-
tudor
- prc1
- biotechnology
-
osterix
- pargyline
- hp1
-
homeodomain
-
fad-dependent
-
nanog
-
non-histone
- pharmacology
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
hide(Overall reactions are displayed. Show all >>)
Synonyms
histone demethylase, kdm3a, jmjd1a, lysine-specific demethylase 1, jmjd2b, jmjd2c, histone lysine demethylase, jmjd2d, kdm3b, jhdm2a, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
H3K9Me3 demethylase
histone H3K9 demethylase
JMJD2B
JMJD2C
Kdm3b
KDM4B
Kdm4c
KDM4D
additional information
additional information
-
the enzyme belongs to the Jumonji C, JmjC, protein family, that is specific for the demethylation of H3K9me1/2
SYSTEMATIC NAME
IUBMB Comments
[histone H3]-N6,N6,N6-trimethyl-L-lysine9,2-oxoglutarate:oxygen oxidoreductase
Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated Lys-9 residues in the tail of the histone protein H3 (H3K9). This lysine residue can exist in three methylation states (mono-, di- and trimethylated), but this group of enzymes only act on the the tri- and di-methylated forms. The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. cf. EC 1.14.11.65, [histone H3]-dimethyl-L-lysine9 demethylase.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
[histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 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,N6-trimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-N6-methyl-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
overall reaction
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + 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-lysine4 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine4 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
preferred target for all KDM4 proteins, in general exhibiting 4fold preference for [histone H3]-N6,N6,N6-trimethyl-L-lysine9 over [histone H3]-N6,N6,N6-trimethyl-L-lysine36. The preference for [histone H3]-N6,N6,N6-trimethyl-L-lysine9 over [histone H3]-N6,N6-dimethyl-L-lysine9 is more modest form KDM4A (less than 3fold), KDM4B (less than 1.5fold), and KDM4D (less than 2.5fold), while the preference for KDM4C is nearly equivalent
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
additional information
?
-
the bifunctional enzyme is active on H3K9me3/me2 and H3K36me3/me2 (EC 1.14.11.69) substrates
-
-
?
additional information
?
-
the bifunctional enzyme is active on H3K9me3/me2 and H3K36me3/me2 (EC 1.14.11.69) substrates
-
-
?
additional information
?
-
the bifunctional enzyme is active on H3K9me3/me2 and H3K36me3/me2 (EC 1.14.11.69) substrates
-
-
?
additional information
?
-
-
the bifunctional enzyme is active on H3K9me3/me2 and H3K36me3/me2 (EC 1.14.11.69) substrates
-
-
?
additional information
?
-
-
LSD1 is a nuclear amine oxidase that utilizes oxygen as an electron acceptor to reduce methylated lysine to form lysine. It demethylates H3K4m1 and H3K4m2, as well as H3K9m1 and H3K9m2 as a removal of the active nethylation mark
-
-
?
additional information
?
-
-
low level of JMJD2b in nucleoli is not associated with the high level of H3K9 methylation in this nuclear region
-
-
?
additional information
?
-
KDM4D can demethylate H3K9me2 and H3K9me3 into H3K9me1 without significant effects on most of the other histone H3 methylation patterns
-
-
?
additional information
?
-
-
KDM4D can demethylate H3K9me2 and H3K9me3 into H3K9me1 without significant effects on most of the other histone H3 methylation patterns
-
-
?
additional information
?
-
mouse Jmjd2b is a histone demethylase that specifically demethylates H3K9
-
-
?
additional information
?
-
the bifunctional enzyme is active on H3K9me3/me2 and H3K36me3/me2 (EC 1.14.11.69) substrates
-
-
?
additional information
?
-
the bifunctional enzyme is active on H3K9me3/me2 and H3K36me3/me2 (EC 1.14.11.69) substrates
-
-
?
additional information
?
-
the bifunctional enzyme is active on H3K9me3/me2 and H3K36me3/me2 (EC 1.14.11.69) substrates
-
-
?
additional information
?
-
-
the bifunctional enzyme is active on H3K9me3/me2 and H3K36me3/me2 (EC 1.14.11.69) substrates
-
-
?
additional information
?
-
the bifunctional enzyme is active on H3K9me3/me2 and H3K36me3/me2 (EC 1.14.11.69) substrates
-
-
?
additional information
?
-
-
isoform KDM4D does not use [histone H3]-N6,N6,N6-trimethyl-L-lysine36 as substrate. All KDM4 proteins show no activity with [histone H3]-N6,N6-dimethyl-L-lysine36
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
[histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2
histone H3 L-lysine9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 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,N6-trimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-N6-methyl-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
overall reaction
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + 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-lysine4 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine4 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2
[histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine9 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine9 + succinate + formaldehyde + CO2
-
preferred target for all KDM4 proteins, in general exhibiting 4fold preference for [histone H3]-N6,N6,N6-trimethyl-L-lysine9 over [histone H3]-N6,N6,N6-trimethyl-L-lysine36. The preference for [histone H3]-N6,N6,N6-trimethyl-L-lysine9 over [histone H3]-N6,N6-dimethyl-L-lysine9 is more modest form KDM4A (less than 3fold), KDM4B (less than 1.5fold), and KDM4D (less than 2.5fold), while the preference for KDM4C is nearly equivalent
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
-
-
?
additional information
?
-
-
LSD1 is a nuclear amine oxidase that utilizes oxygen as an electron acceptor to reduce methylated lysine to form lysine. It demethylates H3K4m1 and H3K4m2, as well as H3K9m1 and H3K9m2 as a removal of the active nethylation mark
-
-
?
additional information
?
-
-
low level of JMJD2b in nucleoli is not associated with the high level of H3K9 methylation in this nuclear region
-
-
?
additional information
?
-
-
isoform KDM4D does not use [histone H3]-N6,N6,N6-trimethyl-L-lysine36 as substrate. All KDM4 proteins show no activity with [histone H3]-N6,N6-dimethyl-L-lysine36
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
histone methyltransferase SUV39h deficiency changes the association between endogenous JMJD2b and various histone marks at chromocenters, overview. The level of full-length JMJD2b at chromocenters was reduced, corresponding to a global decrease in JMJD2b and H3K9me3
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
transient hyperglycemia induces recruitment of LSD1 to gene regulation sites/promoters
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
in wild-type fibroblasts, the chromatin of ribosomal genes, which is dense with H3K9 methylation, lacks JMJD2b-GFP-1086, while mutant and truncated forms of JMJD2b densely occupie the nucleolar compartment
preferential expression of KDM4D (also known as JMJD2D), one of the tridemethylases of H3K9 in the testis
additional information
Kdm3b is highly expressed in the female reproductive organs including ovary, oviduct and uterus
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
recruitment of the Jmjd2 H3K9/H3K36 demethylases to H3K4me3-marked nucleosomes
recruitment of the Jmjd2 H3K9/H3K36 demethylases to H3K4me3-marked nucleosomes
additional information
additional information
Jmjd2a and Jmjd2c both localize to H3K4me3-positive regions. Recruitment of the Jmjd2 H3K9/H3K36 demethylases to H3K4me3-marked nucleosomes
-
additional information
Jmjd2a and Jmjd2c both localize to H3K4me3-positive regions. Recruitment of the Jmjd2 H3K9/H3K36 demethylases to H3K4me3-marked nucleosomes
-
additional information
Jmjd2a and Jmjd2c both localize to H3K4me3-positive regions. Recruitment of the Jmjd2 H3K9/H3K36 demethylases to H3K4me3-marked nucleosomes
-
additional information
-
Jmjd2a and Jmjd2c both localize to H3K4me3-positive regions. Recruitment of the Jmjd2 H3K9/H3K36 demethylases to H3K4me3-marked nucleosomes
-
additional information
Jmjd2a and Jmjd2c both localize to H3K4me3-positive regions. Recruitment of the Jmjd2 H3K9/H3K36 demethylases to H3K4me3-marked nucleosomes
-
additional information
Jmjd2a and Jmjd2c both localize to H3K4me3-positive regions. Recruitment of the Jmjd2 H3K9/H3K36 demethylases to H3K4me3-marked nucleosomes
-
additional information
Jmjd2a and Jmjd2c both localize to H3K4me3-positive regions. Recruitment of the Jmjd2 H3K9/H3K36 demethylases to H3K4me3-marked nucleosomes
-
additional information
-
Jmjd2a and Jmjd2c both localize to H3K4me3-positive regions. Recruitment of the Jmjd2 H3K9/H3K36 demethylases to H3K4me3-marked nucleosomes
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the enzyme belongs to the Jmjd2 family of H3K9/H3K36 histone demethylases
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
physiological function
evolution
the enzyme belongs to the Jmjd2 family of H3K9/H3K36 histone demethylases
malfunction
metabolism
physiological function
additional information
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
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
KDM4A is a epigenetic regulator of osteoblast and adipocyte differentiation. KDM4A expression is upregulated during osteogenesis and adipogenesis of primary marrow stromal cells and stromal ST2 line. Overexpression of wild-type KDM4A promotes adipogenic differentiation and blocks osteogenic differentiation of the progenitor cells. Depletion or inactivation of KDM4A in undifferentiated progenitor cells inhibits the formation of adipocytes and promotes the differentiation of osteoblasts. Overexpression of KDM4A upregulates the expression of secreted frizzled-related protein Sfrp4 and CCAAT/enhancer-binding protein C/ebpalpha. KDM4A directly binds the promoters of Sfrp4 and C/ebpalpha, removes the histone methylation mark H3K9me3, and reduces DNA methylation levels of CpG in promoter regions of C/ebpalpha and Sfrp4. Overexpression of KDM4A inactivates canonical Wnt signaling
malfunction
Kdm3b knockout mice show restricted postnatal growth and female infertility. Kdm3b ablation decreases IGFBP-3 expressed in the kidney by 53% and significantly reduces IGFBP-3 in the blood, which causes an accelerated degradation of IGF-1 and a 36% decrease in circulating IGF-1 concentration. Kdm3b is highly expressed in the female reproductive organs including ovary, oviduct and uterus. Knockout of Kdm3b in female mice causes irregular estrous cycles, decreases 45% of the ovulation capability and 47% of the fertilization rate, and reduces 44% of the uterine decidual response, which are accompanied with a more than 50% decrease in the circulating levels of the 17beta-estradiol. These female reproductive phenotypes are associated with significantly increased levels of H3K9me1/2/3 in the ovary and uterus. Kdm3bKO mice exhibit restricted somatic growth, low levels of circulating IGF-1 and IGFBP-3 and fast degradation of IGF-1. Female Kdm3bKO mice exhibit a severely impaired reproductive function. Knockout of Kdm3b in female mice prolonges their estrous cycles and reduces their ovulation capacity and fertilization efficiency. Phenotype, overview
malfunction
attenuation of Jmjd2b by si RNA, increases expression of Jmjd3, the H3K27me3 demethylase, and of Ccl2, overview. Jmjd2b attenuation inhibits the gene expression of p65, inducible nitric oxide synthase, B cell lymphoma 2, and transforming growth factor beta in Jmjd2b-knockdown NE-4C cells. In NE-4C cells, Jmjd2b attenuation alters the expression of different genes including Notch1, Notch2, Efna5, Cyr61, Efnb2, Tgf-b2, Nodal, Nrp2, Cntfr, Plxnc1, Hivep2, Lef1, Gabrb2, Sema3e, Meis1, and Itgb8, which all experiencing downregulation of more than 2fold
malfunction
Jmjd2c depletion leads to embryonic stem cell differentiation, which is accompanied by a reduction in the expression of embryonic stem cell-specific genes and an induction of lineage marker genes. The level of H3K36Me3 is not significantly affected by Jmjd2c depletion. Knockdown of Jmjd1a does not appreciably affect Jmjd2c and vice versa
malfunction
Jmjd2c is dispensable for embryonic stem cell maintenance and embryogenesis, while 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
Kdm4d-null mice are viable and fertile and do not show any obvious phenotype. But H3K9me3 accumulates significantly in Kdm4d-null round spermatids, and the distribution of methylated H3K9 in germ cells is dramatically changed. Nevertheless, the progression of spermatogenesis and the number of spermatozoa are normal, likely secondary to the earlier nuclear localization of another H3K9 tridemethylase, KDM4B, in Kdm4d-null elongating spermatids
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
-
enzyme Gasc1 hypomorphic mutant mice exhibit abnormal behaviors including hyperactivity, persistence and many types of learning and memory deficits and abnormal synaptic functions such as prolonged long-term potentiation. Reduced expression of enzyme Gasc1 induces an increase in the number of glial fibrillary acidic protein-positive astrocytes from postnatal day 30 to months 2-3
malfunction
loss of enzyme function results in obesity and hyperlipidemia in mice. Loss of enzyme function disrupts beta-adrenergic-stimulated glycerol release and oxygen consumption in brown fat, and decreases fat oxidation and glycerol release in skeletal muscles
metabolism
expression of histone H3 Lys 9 demethylases Jmjd1a (EC 1.14.11.65) and Jmjd2c is positively correlated with the pluripotent state of ES and iPS cells. Jmjd1a and Jmjd2c regulate the global levels of H3K9Me2 and H3K9Me3, respectively
metabolism
hyperglycemia/hyperinsulinemia induces changes in expression of chromatin modifying genes and their regulation by histone modifications, overview. Crosstalk between these histone modifications under hyperinsulinemic/hyperglycemic conditions: no change in H3K9me1 levels at the coding regions of histone H3K9 demethylase (Jmjd2b) and H3K4 demethylase (Aof1), and decreased H3K4me1 levels at Myst4 and Jmjd2b, and increased H3K4me1 levels at Set and Aof1. Levels of H3K9me1 are only changed at histone acetylase (Myst4) and deacetylase (Set), highlighting the role of this modification in regulating histone acetylation only. The chromatin remodelling genes Myst4, Jmjd2b, Set, and Aof1 show similar pattern of change for H3Ac and H3K4me1 on Myst4, Jmjd2b, Aof1 and Set gene promoter regions under both low glucose and high glucose condition after insulin stimulation
physiological function
-
LSD1 is associated with co-repressor complexes and promotes suppression or activation of gene expression, e.g. LSD1 might be associated to cooperative recruitment to the NFkappaB p65 site for activation in hyperglycemia
physiological function
-
JMJD2b histone demethylase antagonizes H3K9me3 in the pericentromeric heterochromatin
physiological function
enzyme Kdm3b is a Jumonji C domain-containing protein that demethylates mono- and dimethylated lysine 9 of histone H3 (H3K9me1 and H3K9me2). Kdm3b-mediated H3K9 demethylation plays essential roles in maintenance of the circulating IGF-1, postnatal somatic growth, circulating 17beta-estradiol, and female reproductive function
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
Jmjd2b, histone-3 lysine-9 di-/tri-methyl (H3K9me2/3) demethylase, is functional following lipopolysaccharide (LPS) treatment and is crucial in multiple signaling pathways and biological processes. Jmjd2b specifically targets the trimethylated lysine 9 of histone H3 (H3K9) for demethylation at pericentric heterochromatin and euchromatin. Jmjd2b plays a role in LPS-mediated inflammation, whith an epigenetic regulation in NE-4C cells. Effect of LPS on cell viability and NO production in NE-4C cells, overview
physiological function
Jmjd2c acts as a positive regulator for Nanog, which encodes for a key transcription factor for self-renewal in ES cells. Jmjd2c is required to reverse the H3K9Me3 marks at the Nanog promoter region and consequently prevents transcriptional repressors HP1 and KAP1 from binding. Jmjd2c regulates expression of Nanog through demethylation of H3K9Me3, overview. The ES cell transcription circuitry is connected to chromatin modulation through H3K9 demethylation in pluripotent cells
physiological function
the testis-enriched histone demethylase, KDM4D, regulates methylation of histone H3 lysine 9 during spermatogenesis in mouse but is dispensable for fertility. Among various methylations of histone H3, methylation of histone H3 lysine 9 (H3K9) by testis-enriched tridemethylase of H3K9 and its regulation are essential for spermatogenesis. Demethylation of H3K9me3 in round spermatids is dispensable for spermatogenesis, possible defects in Kdm4d-null elongating spermatids can be rescued by functional redundancy of the KDM4B demethylase. KDM4D can demethylate H3K9me2 and H3K9me3 into H3K9me1 without significant effects on most of the other histone H3 methylation patterns
physiological function
-
enzyme expression in mice results in hepatic steatosis when fed a high-fat diet, which is accompanied with increased expression of hepatic peroxisome proliferator-activated receptor gamma2 and its steatosis target genes
physiological function
-
enzyme overexpression contributes to the maintenance of a pluripotent state and induces numerous oncogenic effects. KDM4 proteins are a component of the cellular response to postreplicative and exogenous DNA damage
physiological function
-
the enzyme is responsible for histone 3 lysine 9 demethylation at the cyclin E1 promoter, cyclin E1 induction and B cell proliferation
physiological function
the enzyme plays an essential role in regulating metabolic gene expression and normal weight control in mice. The enzyme directly regulates peroxisome proliferator-activated receptor alpha and Ucp1 expression
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
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
KDM4D is a key regulator of adipogenesis in C3H10T1/2 mesenchymal stem cells. The depletion of KDM4D results in impaired differentiation, which can be rescued by exogenous KDM4D, PPARgamma, and C/EBPalpha, but not by C/EBPbeta. KDM4D interacts physically and functionally with both NFIB and MLL1 complex to regulate C/EBPalpha and PPARgamma expression upon adipogenic hormonal induction. KDM4D is dispensable for the binding of both NFIB and MLL1 complex to the target promoters, but the demethylation of trimethylated H3K9 by KDM4D is required for NFIB and MLL1 complex to deposit trimethylated H3K4 and activate PPARgamma and C/EBPalpha expression
additional information
-
in cells with a deficiency in the histone methyltransferase SUV39h, the level of full-length JMJD2b at chromocenters is reduced, corresponding to a global decrease in JMJD2b and H3K9me3. The PHD Zn-fingers and Tudor domains, which are removed in truncated JMJD2b, are responsible for the aberrant JMJD2b function. Nuclear patterns of full-length JMJD2b in comparison with truncated and mutated forms of JMJD2b, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). KDM4A_MOUSE
1064
0
120334
Swiss-Prot
other Location (Reliability: 2)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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
-
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
-
mutant and truncated forms of JMJD2b densely occupy the nucleolar compartment of fibroblasts. The PHD Zn-fingers and Tudor domains are removed in truncated JMJD2b. Nuclear patterns of full-length JMJD2b in comparison with truncated and mutated forms of JMJD2b, overview
additional information
generation of Kdm3b knockout (Kdm3bKO) mice, phenotype, overview. female Kdm3bKO mice exhibit a severely impaired reproductive function, knockout of Kdm3b increases the levels of H3K9me1, H3K9me2 and H3K9me3 in the ovary and uterus. Knockout of Kdm3b in female mice prolonges their estrous cycles and reduces their ovulation capacity and fertilization efficiency
additional information
construction of Jmjd2c knockout embryonic stem cells by RNAi assay, Jmjd2c depletion leads to embryonic stem cell differentiation, which is accompanied by a reduction in the expression of embryonic stem cell-specific genes and an induction of lineage marker genes. The same mutations that disrupt the in vitro Oct4/DNA interactions also abolished the enhancer activities. Knockdown of Jmjd1a does not appreciably affect Jmjd2c and vice versa
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
-
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 Jmjd2b-knockdown (kd) NE-4C cells. Jmjd2b-kd can inhibit the Notch1, IL-1beta, and IL-2 genes by recruiting repressive H3K9me3 to their promoter. attenuation of Jmjd2b by si RNA, increases expression of Jmjd3, the H3K27me3 demethylase, and of Ccl2, overview. Jmjd2b attenuation inhibits the gene expression of p65, inducible nitric oxide synthase, B cell lymphoma 2, and transforming growth factor beta in Jmjd2b-kd NE-4C cells
additional information
-
generation of Jmjd2b-knockdown (kd) NE-4C cells. Jmjd2b-kd can inhibit the Notch1, IL-1beta, and IL-2 genes by recruiting repressive H3K9me3 to their promoter. attenuation of Jmjd2b by si RNA, increases expression of Jmjd3, the H3K27me3 demethylase, and of Ccl2, overview. Jmjd2b attenuation inhibits the gene expression of p65, inducible nitric oxide synthase, B cell lymphoma 2, and transforming growth factor beta in Jmjd2b-kd NE-4C cells
additional information
targeted disruption of KDM4D, a testis-enriched tridemethylase of H3K9. Kdm4d-null mice are viable and fertile and do not show any obvious phenotype, but H3K9me3 accumulates significantly in Kdm4d-null round spermatids, and the distribution of methylated H3K9 in germ cells is dramatically changed, overview. Lack of expression of Kdm4d in spermatogonia is consistent with lack of expression of Kdm4d in germline stem cells
additional information
-
targeted disruption of KDM4D, a testis-enriched tridemethylase of H3K9. Kdm4d-null mice are viable and fertile and do not show any obvious phenotype, but H3K9me3 accumulates significantly in Kdm4d-null round spermatids, and the distribution of methylated H3K9 in germ cells is dramatically changed, overview. Lack of expression of Kdm4d in spermatogonia is consistent with lack of expression of Kdm4d in germline stem cells
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene KDM4A/Jmjd2a, the loci encoding Jmjd2a and Jmjd2c are both located on chromosome 4 about 40 MB apart and are thus expected to co-segregate with a frequency related to the rate of meiotic recombination
expression of full-length GFP-tagged JMJD2b-GFP-1086 and truncated JMJD2b forms in mouse fibroblasts and in Escherichia coli strain DH5alpha
-
gene KDM4C, cloning of the Jmjd2c intronic DNA containing these Oct4-binding sites upstream of or downstream from a luciferase reporter to test for enhancer activity, robust enhancer activity is observed when the constructs is transfected into embryonic stem cells, real-time PCR expression analysis
gene KDM4C/Jmjd2c, the loci encoding Jmjd2a and Jmjd2c are both located on chromosome 4 about 40 MB apart and are thus expected to co-segregate with a frequency related to the rate of meiotic recombination
gene Kdm4d, expression analysis, recombinant expression in HeLa cells, di- and trimethylated H3K9 disappear from KDM4D-positive cells, whereas H3K9me1 were increased by KDM4D expression
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
KDM4A expression is upregulated in phosphatase and tensin homolog knockout mouse prostate tissue
mRNA and protein levels of Jmjd2a are significantly increased in the neurons of mouse undergoing neuropathic pain
upon 4-hydroxytamoxifen treatment, Jmjd2a and Jmjd2b become undetectable by Western blot, while expression levels for other Jmjd2 family members are unaltered
enzyme expression is markedly increased in the liver of high-fat diet-induced obese mice
-
gene Jmjd2c is positively regulated by the ES cell transcription factor Oct4
induction of NF-kappaB and Jmjd2b by long-term lipolysaccharide treatment
Jmjd2c expression is unaffected by 4-hydroxytamoxifen treatment, while Jmjd2a and Jmjd2b are downregulated
upon 4-hydroxytamoxifen treatment, Jmjd2a and Jmjd2b become undetectable by Western blot, while expression levels for other Jmjd2 family members are unaltered
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
biotechnology
continual removal of H3K9 promoter methylation by Jmjd2 demethylases represents a novel mechanism ensuring transcriptional competence and stability of the pluripotent cell identity
medicine
biotechnology
continual removal of H3K9 promoter methylation by Jmjd2 demethylases represents a novel mechanism ensuring transcriptional competence and stability of the pluripotent cell identity
medicine
medicine
JMJD2A responds to neuropathic pain and participates in the maintenance of neuropathic pain. The mRNA and protein levels of Jmjd2a are significantly increased in the neurons of mouse undergoing neuropathic pain. 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
medicine
KDM4A expression is upregulated in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in prostate cancer cells inhibits their proliferation and survival in vivo and vitro. 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
medicine
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 A/B/C triple-knockout. H3.3 G34R preferentially binds KDM4 while simultaneously inhibiting its enzymatic activity
medicine
KDM4D is a key regulator of adipogenesis in C3H10T1/2 mesenchymal stem cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Brasacchio, D.; Okabe, J.; Tikellis, C.; Balcerczyk, A.; George, P.; Baker, E.K.; Calkin, A.C.; Brownlee, M.; Cooper, M.E.; El-Osta, A.
Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that coexist on the lysine tail
Diabetes
58
1229-1236
2009
Homo sapiens, Mus musculus
Bartova, E.; Stixova, L.; Galiova, G.; Harni?arova Horakova, A.; Legartova, S.; Kozubek, S.
Mutant genetic background affects the functional rearrangement and kinetic properties of JMJD2b histone demethylase
J. Mol. Biol.
405
679-695
2011
Mus musculus
Pedersen, M.T.; Kooistra, S.M.; Radzisheuskaya, A.; Laugesen, A.; Johansen, J.V.; Hayward, D.G.; Nilsson, J.; Agger, K.; Helin, K.
Continual removal of H3K9 promoter methylation by Jmjd2 demethylases is vital for ESC self-renewal and early development
EMBO J.
35
1550-1564
2016
Mus musculus (Q8BW72), Mus musculus (Q8VCD7), Mus musculus (Q91VY5), Mus musculus, Mus musculus C57BL/6 (Q8BW72), Mus musculus C57BL/6 (Q8VCD7), Mus musculus C57BL/6 (Q91VY5)
Liu, Z.; Chen, X.; Zhou, S.; Liao, L.; Jiang, R.; Xu, J.
The histone H3K9 demethylase Kdm3b is required for somatic growth and female reproductive function
Int. J. Biol. Sci.
11
494-507
2015
Mus musculus (Q6ZPY7), Mus musculus C57BL/6 (Q6ZPY7)
Gupta, J.; Kumar, S.; Li, J.; Krishna Murthy Karuturi, R.; Tikoo, K.
Histone H3 lysine 4 monomethylation (H3K4me1) and H3 lysine 9 monomethylation (H3K9me1) distribution and their association in regulating gene expression under hyperglycaemic/hyperinsulinemic conditions in 3T3 cells
Biochimie
94
2656-2664
2012
Mus musculus (Q91VY5)
Iwamori, N.; Zhao, M.; Meistrich, M.L.; Matzuk, M.M.
The testis-enriched histone demethylase, KDM4D, regulates methylation of histone H3 lysine 9 during spermatogenesis in the mouse but is dispensable for fertility
Biol. Reprod.
84
1225-1234
2011
Mus musculus (Q3U2K5), Mus musculus
Loh, Y.; Zhang, W.; Chen, X.; George, J.; Ng, H.
Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells
Genes Dev.
21
2545-2557
2007
Mus musculus (Q8VCD7)
Tateishi, K.; Okada, Y.; Kallin, E.; Zhang, Y.
Role of Jhdm2a in regulating metabolic gene expression and obesity resistance
Nature
458
757-761
2009
Mus musculus (Q6PCM1)
Das, N.D.; Choi, M.R.; Jung, K.H.; Park, J.H.; Lee, H.T.; Das, A.; Kim, S.H.; Chai, Y.G.
Functional analysis of histone demethylase Jmjd2b on lipopolysaccharide-treated murine neural stem cells (NSCs)
Neurotox. Res.
23
154-165
2013
Mus musculus (Q91VY5), Mus musculus
Young, L.C.; Hendzel, M.J.
The oncogenic potential of Jumonji D2 (JMJD2/KDM4) histone demethylase overexpression
Biochem. Cell Biol.
91
369-377
2013
Mus musculus
Sudo, G.; Kagawa, T.; Kokubu, Y.; Inazawa, J.; Taga, T.
Increase in GFAP-positive astrocytes in histone demethylase GASC1/KDM4C/JMJD2C hypomorphic mutant mice
Genes Cells
21
218-225
2016
Mus musculus
Jiang, Y.; Li, C.; Wu, Q.; An, P.; Huang, L.; Wang, J.; Chen, C.; Chen, X.; Zhang, F.; Ma, L.; Liu, S.; He, H.; Xie, S.; Sun, Y.; Liu, H.; Zhan, Y.; Tao, Y.; Liu, Z.; Sun, X.; Hu, Y.; Wang, Q.; Ye, D.; Zhang, J.; Zou, S.; Wang, Y.; Wei, G.; Liu, Y.; Shi, Y.; Eugene Chin, Y.; Hao, Y.; Wang, F.; Zhang, X.
Iron-dependent histone 3 lysine 9 demethylation controls B cell proliferation and humoral immune responses
Nat. Commun.
10
2935
2019
Mus musculus
Kim, J.H.; Jung, D.Y.; Nagappan, A.; Jung, M.H.
Histone H3K9 demethylase JMJD2B induces hepatic steatosis through upregulation of PPARgamma2
Sci. Rep.
8
13734
2018
Homo sapiens, Mus musculus
Agger, K.; Nishimura, K.; Miyagi, S.; Messling, J.E.; Rasmussen, K.D.; Helin, K.
The KDM4/JMJD2 histone demethylases are required for hematopoietic stem cell maintenance
Blood
134
1154-1158
2019
Mus musculus (Q91VY5)
Cui, S.Z.; Lei, Z.Y.; Guan, T.P.; Fan, L.L.; Li, Y.Q.; Geng, X.Y.; Fu, D.X.; Jiang, H.W.; Xu, S.H.
Targeting USP1-dependent KDM4A protein stability as a potential prostate cancer therapy
Cancer Sci.
111
1567-1581
2020
Mus musculus (Q8BW72), Mus musculus
Qi, Q.; Wang, Y.; Wang, X.; Yang, J.; Xie, Y.; Zhou, J.; Li, X.; Wang, B.
Histone demethylase KDM4A regulates adipogenic and osteogenic differentiation via epigenetic regulation of C/EBPalpha and canonical Wnt signaling
Cell. Mol. Life Sci.
77
2407-2421
2020
Mus musculus (Q8BW72)
Zhou, J.; Wang, F.; Xu, C.; Zhou, Z.; Zhang, W.
The histone demethylase JMJD2A regulates the expression of BDNF and mediates neuropathic pain in mice
Exp. Cell Res.
361
155-162
2017
Mus musculus (Q8BW72), Mus musculus
Voon, H.P.J.; Udugama, M.; Lin, W.; Hii, L.; Law, R.H.P.; Steer, D.L.; Das, P.P.; Mann, J.R.; Wong, L.H.
Inhibition of a K9/K36 demethylase by an H3.3 point mutation found in paediatric glioblastoma
Nat. Commun.
9
3142
2018
Mus musculus (Q91VY5)
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