1.14.11.68: [histone H3]-trimethyl-L-lysine27 demethylase
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For detailed information about [histone H3]-trimethyl-L-lysine27 demethylase, go to the full flat file.
Word Map on EC 1.14.11.68
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1.14.11.68
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kabuki
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chromatin
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facial
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demethylases
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intellectual
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pik3ca
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arid1a
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crebbp
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h3k4me3
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polycomb
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medicine
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muscle-invasive
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smarca4
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k-specific
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fat1
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gestalt
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gsk-j4
- 1.14.11.68
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kabuki
- chromatin
-
facial
- demethylases
-
intellectual
- pik3ca
-
arid1a
- crebbp
-
h3k4me3
-
polycomb
- medicine
-
muscle-invasive
-
smarca4
-
k-specific
- fat1
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gestalt
- gsk-j4
Reaction
+ 2 2-oxoglutarate + 2 O2 = + 2 succinate + 2 formaldehyde + 2 CO2
Synonyms
F18E9.5, histone demethylase, jmjd-3.1, JMJD3, KDM6A, Kdm6al, KDM6B, KDM6C, lysine-specific demethylase 6A, lysine-specific demethylase 6B, UTX, UTX1, UTY
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General Information
General Information on EC 1.14.11.68 - [histone H3]-trimethyl-L-lysine27 demethylase
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physiological function
at the blastula stage, Jmjd3, Utx and H3K27 methylase Ezh2 show similar expression patterns in the animal cap and marginal zone that give rise to the ectoderm and mesoderm, respectively. The three genes maintain similar expresxadsion patterns in the neural plate, preplacodal ectoderm and axial mesoderm during the gastrula and neurula stages. Later, expression is maintained in the developing brain and cranial sensory tissues, such as the eye and ear, of tailbud embryos
physiological function
both demthylase Utx and Jmjd3 redundantly promote H3K27Me3 removal at, and expression of, a specific subset of genes involved in terminal thymocyte differentiation, especially S1pr1, encoding a sphingosine-phosphate receptor required for thymocyte egress. Thymocyte expression of S1pr1 is not rescued in Jmjd3- and Utx-deficient male mice, which carry the catalytically inactive Utx homolog Uty
physiological function
demethylase UTX mediates removal of H3K27me3 at the Myog and CKm genes. Transactivator Six4 initially recruits UTX to the regulatory region of muscle genes. The resulting loss of H3K27me3 marks is limited to the region upstream of the transcriptional start site. Blocking polymerase Pol II elongation on transcribed genes leads to increased H3K27me3 within the coding region, and formation of bivalent (H3K27me3/H3K4me3) chromatin domains
physiological function
during the monolayer differentiation of mouse embryonic stem cells into neural stem cells, Jmjd3 controls the expression of key regulators and markers of neurogenesis and is required for commitment to the neural lineage. Jmjd3 targets show distinct patterns of H3K27 methylation and expression
physiological function
histone demethylase JMJD3 regulates the expression of neutrophil membrane proteinase 3 (mPR3, EC 3.4.21.76) in lipopolysaccharide-stimulated neutrophils, mostly during the early inflammatory response in sepsis. JMJD3 regulates the expression of mPR3 by changing the level of H3K27me3 in LPS-stimulated neutrophils
physiological function
histone H3 lysine-27 demethylation crucially regulatesT helper cell Th17 differentiation. Activation of naive CD41 T cells immediately induces high expression of Jmjd3. Genetic depletion of Jmjd3 in CD41 T cells specifically impairs Th17 cell differentiation both in vitro and in vivo. Jmjd3-deficient mice are resistant to the induction of experimental autoimmune encephalomyelitis. Inhibition of the H3K27 demethylase activity with the specific inhibitor GSK-J4 dramatically suppresses Th17 cell differentiation in vitro. Jmjd3 directly binds to and reduces the level of H3K27 trimethylation (me3) at the genomic sites of Rorc
physiological function
histone H3K27 demethylase JMJD3 regulates the fragmentation of spermatogonial cysts. Down-regulation of Jmjd3 in spermatogonial stem cells promotes an increase in undifferentiated spermatogonia but does not affect their differentiation. Germ cell-specific Jmjd3 null male mice have larger testes and sire offspring for a longer period compared to controls. Jmjd3 deficiency induces frequent fragmentation of spermatogonial cysts by abscission of intercellular bridges
physiological function
inhibition of Utx1 results in misregulation of hox genes and a striking posterior developmental defect, which is partially rescued by wild-type, but not by catalytically inactive, human Utx
physiological function
JmjC-domain-containing proteins UTX and JMJD3 demethylate tri-methylated Lys 27 on histone H3. Ectopic expression of JMJD3 leads to a strong decrease of H3K27me3 levels and causes delocalization of polycomb proteins in vivo. H3K27me3 demethylation regulated by UTX/JMJD3 proteins is essential for proper development
physiological function
JmjC-domain-containing proteins UTX and JMJD3 demethylate tri-methylated Lys 27 on histone H3. H3K27me3 demethylation regulated by UTX/JMJD3 proteins is essential for proper development
physiological function
JMJD3 is associated with demethylase KIAA1718. JMJD3 and KIAA1718 directly bind to and regulate the expression of a plethora of common target genes in both a demethylase activity-dependent and -independent manner. JMJD3 and KIAA1718 collaborate to demethylate trimethylated H3K27 (H3K27me3) on a subset of their target genes. Reduction of either JMJD3 or KIAA1718 diminishes polymerase Pol II traveling along the gene bodies of the affected genes while having no effect on the promoter-proximal Pol II. JMJD3 and KIAA1718 also play a role in localizing elongation factors SPT6 and SPT16 to the target genes
physiological function
Jmjd3 is expressed in macrophages in response to bacterial products and inflammatory cytokines. Jmjd3 binds PcG target genes and regulates their H3K27me3 levels and transcriptional activity, the activation of Jmjd3 requires NF-kappaB
physiological function
Jmjd3 is involved in brown fat development and white fat browning. A significant subset of brown fat-selective genes, but not common fat genes or white fat-selective genes, are demarcated by H3K27me3 in both brown and white preadipocytes. Jmjd3-catalyzed removal of H3K27me3, in part through Rreb1-mediated recruitment, is required for expression of brown fat-selective genes and for development of beige adipocytes both in vitro and in vivo. Gain- and loss-of-function Jmjd3 transgenic mice show age-dependent body weight reduction and cold intolerance, respectively
physiological function
JMJD3 upregulation and NF-kappaB activation occur in the region of the wound edge during keratinocyte wound healing. JMJD3 interacts with NF-kappaB, resulting in increased expression of the inflammatory matrix metalloproteinase, and growth factor genes via demethylation of H3K27me3 at the gene promoters. Inactivation of JMJD3 or NF-kappaB results in aberrant keratinocyte wound healing
physiological function
loss of Jmjd3 activity causes perinatal lethality with the complete and selective disruption of the pre-Boetzinger complex, the pacemaker of the respiratory rhythm generator. Jmjd3-null mice die at birth of respiratory failure. The enzymatic activity of Jmjd3 is selectively required for the maintenance of the pre-Boetzinger complex and controls critical regulators of pre-Boetzinger complex activity
physiological function
male embryos lacking both H3K27 demethylases Jmjd3 and Utx survive to term. At mid-gestation, embryos demonstrate proper patterning and activation of Hox genes. The embryos retain the Y-chromosome UTtx homolog, UtyY, which cannot demethylate H3K27me3. Embryonic stem cells lacking both Jmjd3 and Utx exhibit a typical decrease in global H3K27me3 levels with differentiation. Retinoic acid differentiations of these embryonic stem cells demonstrate loss of H3K27me3 and gain of H3K4me3 to Hox promoters and other transcription factors, and induce expression similar to control cells. A small subset of genes exhibit decreased expression associated with reduction of promoter H3K4me3 and some low-level accumulation of H3K27me3. Utx and Jmjd3 mutant mouse embryonic fibroblasts demonstrate dramatic loss of H3K27me3 from promoters of several Hox genes and transcription factors
physiological function
microRNA miR-142-3p binds directly to lysine demethylase 6A (KDM6A), which results in demethylation of H3K27me3 and in turn upregulated expression of the anti-apoptotic protein Bcl-2. miR-142-3p knockdown increases autophagy-related protein 16-1-mediated autophagy in in vitro induced human regulatory T cells
physiological function
mutation of JMJD3 orthologue, or inhibition of its expression, results in abnormal gonad development
physiological function
RNAi inhibition of UTX leads to increased H3K27me3 levels at some HOX gene promoters
physiological function
the apoptosis rate of cardiomyocytes is significantly exacerbated when Kdm6a is knocked down. The expression of the Na+/Ca2+ exchanger Ncx is significantly upregulated in cardiomyocytes under hypoxia. Knockdown of Kdm6a downregulates the Ncx expression via enhancing H3K27me3 modification on Ncx gene promoter, and attenuates the intracellular calcium-influx ability in cardiomyocytes as a consequence
physiological function
transfection of JMJD3 into HeLa cells causes a specific reduction of trimethyl H3K27, but has no effect on di- and monomethyl H3K27, or histone lysine methylations on H3K4 and H3K9. The enzymatic activity requires the JmjC domain. JMJD3 directly catalyzes the demethylation
physiological function
UTX occupies the promoters of HOX gene clusters and regulates their transcriptional output by modulating the recruitment of polycomb repressive complex 1 and the monoubiquitination of histone H2A. UTX associates with mixed-lineage leukemia 2/3 complexes, and during retinoic acid signaling events, the recruitment of the UTX complex to HOX genes results in H3K27 demethylation and a concomitant methylation of H3K4
physiological function
UTX specifically removes methyl marks on H3K27 in vitro. The demethylase activity of UTX requires a catalytically active JmjC domain. Overexpression of UTX leads to reduced di- and trimethylation on H3K27 in cells