Enhancer Of Zeste Homolog 2 (EZH2)

ENX-1; KMT6; KMT6A; Histone-lysine N-methyltransferase EZH2; Lysine N-methyltransferase 6

SPN	N666
HGNC	3527
MGI	107940
PubMed	24867641
RGD	1595860
UniProt	Q15910
Wiki	EZH2

EZH2 encodes a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. EZH2 acts mainly as a gene silencer; it performs this role by the addition of three methyl groups to Lysine 27 of histone 3, a modification leading to chromatin condensation.

This protein associates with the embryonic ectoderm development protein, the VAV1 oncoprotein, and the X-linked nuclear protein (XNP). This protein may play a role in the hematopoietic and central nervous systems. Two transcript variants encoding distinct isoforms have been identified for this gene.

Reference

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Genomics 38:30-37(1996) [PubMed] [Europe PMC] [Abstract]

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Mol. Cell. Biol. 16:3066-3073(1996) [PubMed] [Europe PMC] [Abstract]

"Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein."
Hum. Mol. Genet. 7:679-684(1998) [PubMed] [Europe PMC] [Abstract]

"Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes."
Mol. Cell. Biol. 18:3586-3595(1998) [PubMed] [Europe PMC] [Abstract]

"Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation."
Nat. Genet. 23:474-478(1999) [PubMed] [Europe PMC] [Abstract]

"The polycomb group protein EED interacts with YY1, and both proteins induce neural tissue in Xenopus embryos."
Mol. Cell. Biol. 21:1360-1369(2001) [PubMed] [Europe PMC] [Abstract]

"Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein."
Genes Dev. 16:2893-2905(2002) [PubMed] [Europe PMC] [Abstract]

"Selective interactions between vertebrate polycomb homologs and the SUV39H1 histone lysine methyltransferase suggest that histone H3-K9 methylation contributes to chromosomal targeting of Polycomb group proteins."
Mol. Cell. Biol. 22:5539-5553(2002) [PubMed] [Europe PMC] [Abstract]

"Role of histone H3 lysine 27 methylation in Polycomb-group silencing."
Science 298:1039-1043(2002) [PubMed] [Europe PMC] [Abstract]

"EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer."
EMBO J. 22:5323-5335(2003) [PubMed] [Europe PMC] [Abstract]

"Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity."
EMBO J. 23:4061-4071(2004) [PubMed] [Europe PMC] [Abstract]

"Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27."
Genes Dev. 18:1592-1605(2004) [PubMed] [Europe PMC] [Abstract]

"Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3."
Mol. Cell 14:183-193(2004) [PubMed] [Europe PMC] [Abstract]

"SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex."
Mol. Cell 15:57-67(2004) [PubMed] [Europe PMC] [Abstract]

"Activated p53 suppresses the histone methyltransferase EZH2 gene."
Oncogene 23:5759-5769(2004) [PubMed] [Europe PMC] [Abstract]

"The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling."
Cell 122:835-847(2005) [PubMed] [Europe PMC] [Abstract]

"Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation."
Proc. Natl. Acad. Sci. U.S.A. 102:1859-1864(2005) [PubMed] [Europe PMC] [Abstract]

"Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3."
Science 310:306-310(2005) [PubMed] [Europe PMC] [Abstract]

"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]

"Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions."
Genes Dev. 20:1123-1136(2006) [PubMed] [Europe PMC] [Abstract]

"Substrate preferences of the EZH2 histone methyltransferase complex."
J. Biol. Chem. 281:8365-8370(2006) [PubMed] [Europe PMC] [Abstract]

"The polycomb group protein EZH2 is required for mammalian circadian clock function."
J. Biol. Chem. 281:21209-21215(2006) [PubMed] [Europe PMC] [Abstract]

"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]

"The Polycomb group protein EZH2 directly controls DNA methylation."
Nature 439:871-874(2006) [PubMed] [Europe PMC] [Abstract]

Erratum
Nature 446:824-824(2006)

"Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells."
Nat. Struct. Mol. Biol. 13:793-797(2006) [PubMed] [Europe PMC] [Abstract]

"pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene."
Genes Dev. 21:49-54(2007) [PubMed] [Europe PMC] [Abstract]

"The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells."
Genes Dev. 21:525-530(2007) [PubMed] [Europe PMC] [Abstract]

"Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer."
Nat. Genet. 39:232-236(2007) [PubMed] [Europe PMC] [Abstract]

"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]

"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]

"Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms."
Mol. Cell 32:503-518(2008) [PubMed] [Europe PMC] [Abstract]

"Role of hPHF1 in H3K27 methylation and Hox gene silencing."
Mol. Cell. Biol. 28:1862-1872(2008) [PubMed] [Europe PMC] [Abstract]

"Ezh2 requires PHF1 to efficiently catalyze H3 lysine 27 trimethylation in vivo."
Mol. Cell. Biol. 28:2718-2731(2008) [PubMed] [Europe PMC] [Abstract]

"The polycomb repressive complex 2 is a potential target of SUMO modifications."
PLoS ONE 3:E2704-E2704(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]

"Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2."
Nat. Cell Biol. 12:1108-1114(2010) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"Corepressor protein CDYL functions as a molecular bridge between polycomb repressor complex 2 and repressive chromatin mark trimethylated histone lysine 27."
J. Biol. Chem. 286:42414-42425(2011) [PubMed] [Europe PMC] [Abstract]

"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]

"EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex."
Mol. Cell 48:572-586(2012) [PubMed] [Europe PMC] [Abstract]

"O-GlcNAcylation regulates EZH2 protein stability and function."
Proc. Natl. Acad. Sci. U.S.A. 111:1355-1360(2014) [PubMed] [Europe PMC] [Abstract]

"Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin."
Nat. Genet. 42:181-185(2010) [PubMed] [Europe PMC] [Abstract]

"Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A."
Blood 118:3932-3941(2011) [PubMed] [Europe PMC] [Abstract]

"Mutations in EZH2 cause Weaver syndrome."
Am. J. Hum. Genet. 90:110-118(2012) [PubMed] [Europe PMC] [Abstract]