EZH2

From Wikipedia, the free encyclopedia
Enhancer of zeste homolog 2 (Drosophila)
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsEZH2; ENX-1; ENX1; EZH1; KMT6; KMT6A; WVS2
External IDsOMIM: 601573 MGI: 107940 HomoloGene: 37926 GeneCards: EZH2 Gene
EC number2.1.1.43
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez214614056
EnsemblENSG00000106462ENSMUSG00000029687
UniProtQ15910Q61188
RefSeq (mRNA)NM_001203247NM_001146689
RefSeq (protein)NP_001190176NP_001140161
Location (UCSC)Chr 7:
148.5 – 148.58 Mb		Chr 6:
47.53 – 47.6 Mb
PubMed search
This box:

Histone-lysine N-methyltransferase EZH2 is an enzyme that in humans is encoded by the EZH2 gene.[1][2] Two transcript variants encoding distinct isoforms have been identified for this gene.[3]

Function

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.[4]

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.[3]

Clinical significance

Mutations in the EZH2 gene cause Weaver syndrome.[5]

The microRNA miR-101 normally inhibits translation of the messenger RNA coding for EZH2. Loss of this microRNA gene therefore leads to increased production of EZH2.[6]

EZH2 over expression may promote cancer due to increase in histone methylation which silence the expression of tumor suppressor genes. An EZH2-targeting drug inhibits the progression of brain and prostate cancer in pre-clinical models.[7][8]

Interactions

EZH2 has been shown to interact with:


References

  1. ↑ Chen H, Rossier C, Antonarakis SE (Mar 1997). "Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2". Genomics 38 (1): 30–7. doi:10.1006/geno.1996.0588. PMID 8954776. 
  2. ↑ Fiskus W, Pranpat M, Balasis M, Herger B, Rao R, Chinnaiyan A, Atadja P, Bhalla K (Dec 2006). "Histone deacetylase inhibitors deplete enhancer of zeste 2 and associated polycomb repressive complex 2 proteins in human acute leukemia cells". Mol Cancer Ther 5 (12): 3096–104. doi:10.1158/1535-7163.MCT-06-0418. PMID 17172412. 
  3. ↑ 3.0 3.1 "Entrez Gene: EZH2 enhancer of zeste homolog 2 (Drosophila)". 
  4. ↑ Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones RS, Zhang Y. (NOV 2002). "Role of histone H3 lysine 27 methylation in Polycomb-group silencing". Science 298 (5595): 1039–43. doi:10.1126/science.1076997. PMID 12351676. 
  5. ↑ Gibson WT, Hood RL, Zhan SH, Bulman DE, Fejes AP, Moore R, Mungall AJ, Eydoux P, Babul-Hirji R, An J, Marra MA, Chitayat D, Boycott KM, Weaver DD, Jones SJ (December 2011). "Mutations in EZH2 Cause Weaver Syndrome". Am J Hum Genet 90 (1): 110–8. doi:10.1016/j.ajhg.2011.11.018. PMID 22177091. 
  6. ↑ Smits M, Nilsson J, Mir SE, van der Stoop PM, Hulleman E, Niers JM, de Witt Hamer PC, Marquez VE, Cloos J, Krichevsky AM, Noske DP, Tannous BA, Würdinger T (December 2010). "miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis". Oncotarget 1 (8): 710–20. PMC 3124376. PMID 21321380. 
  7. ↑ Suvà ML, Riggi N, Janiszewska M, Radovanovic I, Provero P, Stehle JC, Baumer K, Le Bitoux MA, Marino D, Cironi L, Marquez VE, Clément V, Stamenkovic I (December 2009). "EZH2 is essential for glioblastoma cancer stem cell maintenance". Cancer Res. 69 (24): 9211–8. doi:10.1158/0008-5472.CAN-09-1622. PMID 19934320. 
  8. ↑ Crea F, Hurt EM, Mathews LA, Cabarcas SM, Sun L, Marquez VE, Danesi R, Farrar WL (2011). "Pharmacologic disruption of Polycomb Repressive Complex 2 inhibits tumorigenicity and tumor progression in prostate cancer". Mol. Cancer 10: 40. doi:10.1186/1476-4598-10-40. PMC 3100246. PMID 21501485. 
  9. ↑ Cardoso C, Timsit S, Villard L, Khrestchatisky M, Fontès M, Colleaux L (April 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. 
  10. ↑ van Lohuizen M, Tijms M, Voncken JW, Schumacher A, Magnuson T, Wientjens E (June 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. 
  11. ↑ Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K (October 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. 
  12. ↑ 12.0 12.1 van der Vlag J, Otte AP (December 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. 
  13. ↑ Hobert O, Jallal B, Ullrich A (June 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. 

Further reading

Transcriptional regulation
prokaryotic
eukaryotic
Histone-modifying enzymes
(histone/nucleosome):
DNA methylation:
Chromatin remodeling:
both
Promotion
Initiation (bacterial,
eukaryotic
Elongation
Termination
(bacterial,
eukaryotic)
see also disorders of transcription and post transcriptional modification
B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)
This article is issued from Wikipedia. The text is available under the Creative Commons Attribution/Share Alike; additional terms may apply for the media files.