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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
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 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
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
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
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
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
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De Santa, F.; Totaro, M.G.; Prosperini, E.; Notarbartolo, S.; Testa, G.; Natoli, G.
The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing
Cell
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1083-1094
2007
Mus musculus (Q5NCY0)
brenda
Burgold, T.; Voituron, N.; Caganova, M.; Tripathi, P.P.; Menuet, C.; Tusi, B.K.; Spreafico, F.; Bevengut, M.; Gestreau, C.; Buontempo, S.; Simeone, A.; Kruidenier, L.; Natoli, G.; Casola, S.; Hilaire, G.; Testa, G.
The H3K27 demethylase JMJD3 is required for maintenance of the embryonic respiratory neuronal network, neonatal breathing, and survival
Cell Rep.
2
1244-1258
2012
Mus musculus (Q5NCY0)
brenda
Pan, D.; Huang, L.; Zhu, L.J.; Zou, T.; Ou, J.; Zhou, W.; Wang, Y.X2
Jmjd3-mediated H3K27me3 dynamics orchestrate brown fat development and regulate white fat plasticity
Dev. Cell
35
568-583
2015
Mus musculus (Q5NCY0)
brenda
Seenundun, S.; Rampalli, S.; Liu, Q.C.; Aziz, A.; Palii, C.; Hong, S.; Blais, A.; Brand, M.; Ge, K.; Dilworth, F.J.
UTX mediates demethylation of H3K27me3 at muscle-specific genes during myogenesis
EMBO J.
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1401-1411
2010
Mus musculus (O70546)
brenda
Kamikawa, Y.F.; Donohoe, M.E.
The localization of histone H3K27me3 demethylase Jmjd3 is dynamically regulated
Epigenetics
9
834-841
2014
Homo sapiens (O15054), Mus musculus (Q5NCY0)
brenda
Liu, Z.; Cao, W.; Xu, L.; Chen, X.; Zhan, Y.; Yang, Q.; Liu, S.; Chen, P.; Jiang, Y.; Sun, X.; Tao, Y.; Hu, Y.; Li, C.; Wang, Q.; Wang, Y.; Chen, C.D.; Shi, Y.; Zhang, X.
The histone H3 lysine-27 demethylase Jmjd3 plays a critical role in specific regulation of Th17 cell differentiation
J. Mol. Cell Biol.
7
505-516
2015
Mus musculus (Q5NCY0)
brenda
Messer, H.G.; Jacobs, D.; Dhummakupt, A.; Bloom, D.C.
Inhibition of H3K27me3-specific histone demethylases JMJD3 and UTX blocks reactivation of herpes simplex virus 1 in trigeminal ganglion neurons
J. Virol.
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3417-3420
2015
Mus musculus (O70546), Mus musculus (Q5NCY0)
brenda
Manna, S.; Kim, J.; Bauge, C.; Cam, M.; Zhao, Y.; Shetty, J.; Vacchio, M.; Castro, E.; Tran, B.; Tessarollo, L.; Bosselut, R.
Histone H3 lysine 27 demethylases Jmjd3 and Utx are required for T-cell differentiation
Nat. Commun.
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8152
2015
Mus musculus (Q5NCY0)
brenda
Shpargel, K.B.; Starmer, J.; Yee, D.; Pohlers, M.; Magnuson, T.
KDM6 demethylase independent loss of histone H3 lysine 27 trimethylation during early embryonic development
PLoS Genet.
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e1004507
2014
Mus musculus (O70546), Mus musculus (Q5NCY0)
brenda
Burgold, T.; Spreafico, F.; De Santa, F.; Totaro, M.; Prosperini, E.; Natoli, G.; Testa, G.
The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment
PLoS ONE
3
e3404
2008
Mus musculus (Q5NCY0)
brenda
Das, N.; Jung, K.; Chai, Y.
The role of NF-kappaB and H3K27me3 demethylase, Jmjd3, on the anthrax lethal toxin tolerance of RAW 264.7 cells
PLoS ONE
5
e9913
2010
Mus musculus (Q5NCY0)
brenda
Iwamori, N.; Iwamori, T.; Matzuk, M.M.
H3K27 demethylase, JMJD3, regulates fragmentation of spermatogonial cysts
PLoS One
8
e72689
2013
Mus musculus (Q5NCY0)
brenda