EZH2

Enhancer of zeste homolog 2 (Drosophila)
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2C6V
Identifiers
Symbols	EZH2; ENX-1; ENX1; EZH1; KMT6; KMT6A; WVS2
External IDs	OMIM: 601573 MGI: 107940 HomoloGene: 37926 GeneCards: EZH2 Gene
EC number	2.1.1.43
Gene Ontology Molecular function • core promoter binding • DNA binding • chromatin binding • protein binding • histone-lysine N-methyltransferase activity • histone methyltransferase activity • sequence-specific DNA binding Cellular component • ESC/E(Z) complex • pronucleus Biological process • S phase of mitotic cell cycle • regulation of protein phosphorylation • chromatin organization • transcription, DNA-dependent • regulation of transcription, DNA-dependent • regulation of gliogenesis • cerebellar cortex development • negative regulation of transcription elongation from RNA polymerase II promoter • regulation of cell proliferation • negative regulation of epidermal cell differentiation • negative regulation of transcription, DNA-dependent • negative regulation of retinoic acid receptor signaling pathway • negative regulation of striated muscle cell differentiation • G1 to G0 transition • histone H3-K27 methylation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2146	14056
Ensembl	ENSG00000106462	ENSMUSG00000029687
UniProt	Q15910	Q61188
RefSeq (mRNA)	NM_001203247	NM_001146689
RefSeq (protein)	NP_001190176	NP_001140161
Location (UCSC)	Chr 7: 148.5 – 148.58 Mb	Chr 6: 47.53 – 47.6 Mb
PubMed search	[1]	[2]

Histone-lysine N-methyltransferase EZH2 is an enzyme that in humans is encoded by the EZH2 gene.

This gene 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.

Clinical significance

Mutations in in the EZH2 gene cause Weaver syndrome.

EZH2 overproduction may cause cancer due to increase in histone methylation. This histone methylation may play a role in silencing the expression of tumor suppressor genes, which may cause certain cancers. The microRNA produced by miR-101 normally inhibits translation of the messenger RNA coding for EZH2. Loss of this microRNA gene therefore leads to increased production of EZH2.

Interactions

EZH2 has been shown to interact with:

• ATRX,
• EED,
• HDAC1,
• Histone deacetylase 2, and
• VAV1.

Further reading

• Zeidler M, Kleer CG (2007). "The Polycomb group protein Enhancer of Zeste 2: its links to DNA repair and breast cancer.". J. Mol. Histol. 37 (5-7): 219–23. doi:10.1007/s10735-006-9042-9. PMID 16855786. 
• De Haan G, Gerrits A (2007). "Epigenetic control of hematopoietic stem cell aging the case of Ezh2.". Ann. N. Y. Acad. Sci. 1106 (1): 233–9. doi:10.1196/annals.1392.008. PMID 17332078. 
• Hobert O, Jallal B, Ullrich A (1996). "Interaction of Vav with ENX-1, a putative transcriptional regulator of homeobox gene expression.". Mol. Cell. Biol. 16 (6): 3066–73. PMC 231301. PMID 8649418. 
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548. 
• Abel KJ, Brody LC, Valdes JM, et al. (1997). "Characterization of EZH1, a human homolog of Drosophila Enhancer of zeste near BRCA1.". Genomics 37 (2): 161–71. doi:10.1006/geno.1996.0537. PMID 8921387. 
• Laible G, Wolf A, Dorn R, et al. (1997). "Mammalian homologues of the Polycomb-group gene Enhancer of zeste mediate gene silencing in Drosophila heterochromatin and at S. cerevisiae telomeres.". EMBO J. 16 (11): 3219–32. doi:10.1093/emboj/16.11.3219. PMC 1169939. PMID 9214638. 
• Cardoso C, Timsit S, Villard L, et al. (1998). "Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein.". Hum. Mol. Genet. 7 (4): 679–84. doi:10.1093/hmg/7.4.679. PMID 9499421. 
• van Lohuizen M, Tijms M, Voncken JW, et al. (1998). "Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes.". Mol. Cell. Biol. 18 (6): 3572–9. PMC 108938. PMID 9584197. 
• Sewalt RG, van der Vlag J, Gunster MJ, et al. (1998). "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 (6): 3586–95. PMC 108940. PMID 9584199. 
• Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K (1998). "Point mutations in the WD40 domain of Eed block its interaction with Ezh2.". Mol. Cell. Biol. 18 (10): 5634–42. PMC 109149. PMID 9742080. 
• van der Vlag J, Otte AP (1999). "Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation.". Nat. Genet. 23 (4): 474–8. doi:10.1038/70602. PMID 10581039. 
• Cardoso C, Mignon C, Hetet G, et al. (2000). "The human EZH2 gene: genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders.". Eur. J. Hum. Genet. 8 (3): 174–80. doi:10.1038/sj.ejhg.5200439. PMID 10780782. 
• Raaphorst FM, Otte AP, van Kemenade FJ, et al. (2001). "Distinct BMI-1 and EZH2 expression patterns in thymocytes and mature T cells suggest a role for Polycomb genes in human T cell differentiation.". J. Immunol. 166 (10): 5925–34. PMID 11342607. 
• O'Connell S, Wang L, Robert S, et al. (2001). "Polycomblike PHD fingers mediate conserved interaction with enhancer of zeste protein.". J. Biol. Chem. 276 (46): 43065–73. doi:10.1074/jbc.M104294200. PMID 11571280. 
• Varambally S, Dhanasekaran SM, Zhou M, et al. (2002). "The polycomb group protein EZH2 is involved in progression of prostate cancer.". Nature 419 (6907): 624–9. doi:10.1038/nature01075. PMID 12374981. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
• Scherer SW, Cheung J, MacDonald JR, et al. (2003). "Human chromosome 7: DNA sequence and biology.". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205. 
• Hillier LW, Fulton RS, Fulton LA, et al. (2003). "The DNA sequence of human chromosome 7.". Nature 424 (6945): 157–64. doi:10.1038/nature01782. PMID 12853948. 
• Kleer CG, Cao Q, Varambally S, et al. (2003). "EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells.". Proc. Natl. Acad. Sci. U.S.A. 100 (20): 11606–11. doi:10.1073/pnas.1933744100. PMC 208805. PMID 14500907.