The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

EZH2  -  enhancer of zeste 2 polycomb repressive...

Homo sapiens

Synonyms: ENX-1, ENX1, EZH1, EZH2b, Enhancer of zeste homolog 2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of EZH2

  • The polycomb group protein EZH2 is involved in progression of prostate cancer [1].
  • Recent studies have revealed the intrinsic histone methyltransferase (HMTase) activity of the EED-EZH2 complex and its role in Hox gene silencing, X inactivation, and cancer metastasis [2].
  • Upon removal of p16(INK4A) activity in primary human mammary epithelial cells, polycomb repressors, EZH2 and SUZ12, are up-regulated and recruited to HOXA9, a locus expressed during normal breast development and epigenetically silenced in breast cancer [3].
  • This is the first demonstration that EZH2 expression can be upregulated in fresh lymphoma cells [4].
  • The Polycomb group protein EZH2 is upregulated in proliferating, cultured human mantle cell lymphoma [4].
  • Our data therefore reveal that EZH2 contributes to silencing of IFN-gamma-inducible transcription of MHC2TA in uveal melanoma cells [5].

High impact information on EZH2

  • This chromatin mark is established on these unmethylated CpG island genes early in development and then maintained in differentiated cell types by the presence of an EZH2-containing Polycomb complex [6].
  • Gene silencing mediated by EZH2 requires the SET domain and is attenuated by inhibiting histone deacetylase activity [1].
  • Small interfering RNA (siRNA) duplexes targeted against EZH2 reduce the amounts of EZH2 protein present in prostate cells and also inhibit cell proliferation in vitro [1].
  • Here, we demonstrate that Polycomb genes EZH2 and BMI1 repress p16 expression in human and mouse primary cells, but not in cells deficient for pRB protein function [7].
  • Importantly, recruitment of Suz12, Ezh2 and Eed to target promoters coincides with methylation of histone H3 on Lys 27 [8].

Biological context of EZH2

  • Here we show, through gene expression profiling, that the polycomb group protein enhancer of zeste homolog 2 (EZH2) is overexpressed in hormone-refractory, metastatic prostate cancer [1].
  • Significantly, we propose that EZH2 is a bona fide oncogene, since we find that ectopic expression of EZH2 is capable of providing a proliferative advantage to primary cells and, in addition, its gene locus is specifically amplified in several primary tumors [9].
  • Activated p53 suppressed EZH2 gene expression through repression of the EZH2 gene promoter [10].
  • This suggests a possible causal effect between EZH2 upregulation and increased proliferation in haematopoietic cells [4].
  • Poorly differentiated invasive carcinoma displayed an enhanced rate of cell division within BMI-1/EZH2 double-positive cells [11].

Anatomical context of EZH2

  • In the B cell-derived Ramos cell line, EZH2 overexpression caused an increase in the proliferation rate [4].
  • YY1 and EZH2 transcripts were additionally detected in metaphase II oocytes [12].
  • Our data show that BMI-1 and EZH2 expression in mature peripheral T cells is mutually exclusive and linked to proliferation status, and that this pattern is not yet established in thymocytes of the cortex and medulla [13].
  • By contrast, subcapsular immature double-negative (DN) (CD4(-)/CD8(-)) T cells in the thymus coexpressed BMI-1 and EZH2 or were BMI-1 single positive [13].
  • Although EZH2 expression was significant in univariate survival analysis, only tumor cell proliferation and lymph node status were significant in the final multivariate model [14].

Associations of EZH2 with chemical compounds


Physical interactions of EZH2

  • The EED/EZH2 PcG complex utilizes histone deacetylation to repress gene activity [19].
  • RESULTS: Moderate or strong expression of EZH2 coupled with at most moderate expression of ECAD (i.e., a positive EZH2:ECAD status) was the biomarker combination that was most strongly associated with the recurrence of prostate cancer [20].

Regulatory relationships of EZH2


Other interactions of EZH2

  • SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex [2].
  • Furthermore, we identified the proliferation-specific PcG, EZH2, as an EPC1-interacting protein [22].
  • Suppression of EZH2 expression in tumors by p53 may lead to novel approaches to control cancer progression [10].
  • However, poorly differentiated DCIS and invasive carcinomas frequently expressed EZH2 in combination with HPC-HPH/PRC1 proteins [11].
  • When these results are considered together with published data on EZH2 and on the E2F3 control protein pRB, we conclude that the pRB-E2F3-EZH2 control axis may have a critical role in modulating aggressiveness of individual human prostate cancer [23].

Analytical, diagnostic and therapeutic context of EZH2


  1. The polycomb group protein EZH2 is involved in progression of prostate cancer. Varambally, S., Dhanasekaran, S.M., Zhou, M., Barrette, T.R., Kumar-Sinha, C., Sanda, M.G., Ghosh, D., Pienta, K.J., Sewalt, R.G., Otte, A.P., Rubin, M.A., Chinnaiyan, A.M. Nature (2002) [Pubmed]
  2. SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex. Cao, R., Zhang, Y. Mol. Cell (2004) [Pubmed]
  3. Tumor suppressor p16INK4A regulates polycomb-mediated DNA hypermethylation in human mammary epithelial cells. Reynolds, P.A., Sigaroudinia, M., Zardo, G., Wilson, M.B., Benton, G.M., Miller, C.J., Hong, C., Fridlyand, J., Costello, J.F., Tlsty, T.D. J. Biol. Chem. (2006) [Pubmed]
  4. The Polycomb group protein EZH2 is upregulated in proliferating, cultured human mantle cell lymphoma. Visser, H.P., Gunster, M.J., Kluin-Nelemans, H.C., Manders, E.M., Raaphorst, F.M., Meijer, C.J., Willemze, R., Otte, A.P. Br. J. Haematol. (2001) [Pubmed]
  5. A role for EZH2 in silencing of IFN-gamma inducible MHC2TA transcription in uveal melanoma. Holling, T.M., Bergevoet, M.W., Wilson, L., Van Eggermond, M.C., Schooten, E., Steenbergen, R.D., Snijders, P.J., Jager, M.J., Van den Elsen, P.J. J. Immunol. (2007) [Pubmed]
  6. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Schlesinger, Y., Straussman, R., Keshet, I., Farkash, S., Hecht, M., Zimmerman, J., Eden, E., Yakhini, Z., Ben-Shushan, E., Reubinoff, B.E., Bergman, Y., Simon, I., Cedar, H. Nat. Genet. (2007) [Pubmed]
  7. pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4a tumor suppressor gene. Kotake, Y., Cao, R., Viatour, P., Sage, J., Zhang, Y., Xiong, Y. Genes Dev. (2007) [Pubmed]
  8. Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27. Kirmizis, A., Bartley, S.M., Kuzmichev, A., Margueron, R., Reinberg, D., Green, R., Farnham, P.J. Genes Dev. (2004) [Pubmed]
  9. EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. Bracken, A.P., Pasini, D., Capra, M., Prosperini, E., Colli, E., Helin, K. EMBO J. (2003) [Pubmed]
  10. Activated p53 suppresses the histone methyltransferase EZH2 gene. Tang, X., Milyavsky, M., Shats, I., Erez, N., Goldfinger, N., Rotter, V. Oncogene (2004) [Pubmed]
  11. Poorly differentiated breast carcinoma is associated with increased expression of the human polycomb group EZH2 gene. Raaphorst, F.M., Meijer, C.J., Fieret, E., Blokzijl, T., Mommers, E., Buerger, H., Packeisen, J., Sewalt, R.A., Otte, A.P., van Diest, P.J. Neoplasia (2003) [Pubmed]
  12. Expression of Polycomb-group genes in human ovarian follicles, oocytes and preimplantation embryos. Hinkins, M., Huntriss, J., Miller, D., Picton, H.M. Reproduction (2005) [Pubmed]
  13. Distinct BMI-1 and EZH2 expression patterns in thymocytes and mature T cells suggest a role for Polycomb genes in human T cell differentiation. Raaphorst, F.M., Otte, A.P., van Kemenade, F.J., Blokzijl, T., Fieret, E., Hamer, K.M., Satijn, D.P., Meijer, C.J. J. Immunol. (2001) [Pubmed]
  14. Expression of enhancer of zeste homologue 2 is significantly associated with increased tumor cell proliferation and is a marker of aggressive breast cancer. Collett, K., Eide, G.E., Arnes, J., Stefansson, I.M., Eide, J., Braaten, A., Aas, T., Otte, A.P., Akslen, L.A. Clin. Cancer Res. (2006) [Pubmed]
  15. Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity. Pasini, D., Bracken, A.P., Jensen, M.R., Lazzerini Denchi, E., Helin, K. EMBO J. (2004) [Pubmed]
  16. The polycomb group protein EZH2 is required for mammalian circadian clock function. Etchegaray, J.P., Yang, X., DeBruyne, J.P., Peters, A.H., Weaver, D.R., Jenuwein, T., Reppert, S.M. J. Biol. Chem. (2006) [Pubmed]
  17. EZH2 promotes proliferation and invasiveness of prostate cancer cells. Bryant, R.J., Cross, N.A., Eaton, C.L., Hamdy, F.C., Cunliffe, V.T. Prostate (2007) [Pubmed]
  18. Proliferative involvement of ENX-1, a putative human polycomb group gene, in haematopoietic cells. Fukuyama, T., Otsuka, T., Shigematsu, H., Uchida, N., Arima, F., Ohno, Y., Iwasaki, H., Fukuda, T., Niho, Y. Br. J. Haematol. (2000) [Pubmed]
  19. 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. Sewalt, R.G., Lachner, M., Vargas, M., Hamer, K.M., den Blaauwen, J.L., Hendrix, T., Melcher, M., Schweizer, D., Jenuwein, T., Otte, A.P. Mol. Cell. Biol. (2002) [Pubmed]
  20. Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer. Rhodes, D.R., Sanda, M.G., Otte, A.P., Chinnaiyan, A.M., Rubin, M.A. J. Natl. Cancer Inst. (2003) [Pubmed]
  21. Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2 complex and histone deacetylase in prostate cancer. Chen, H., Tu, S.W., Hsieh, J.T. J. Biol. Chem. (2005) [Pubmed]
  22. A novel repressive E2F6 complex containing the polycomb group protein, EPC1, that interacts with EZH2 in a proliferation-specific manner. Attwooll, C., Oddi, S., Cartwright, P., Prosperini, E., Agger, K., Steensgaard, P., Wagener, C., Sardet, C., Moroni, M.C., Helin, K. J. Biol. Chem. (2005) [Pubmed]
  23. Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome. Foster, C.S., Falconer, A., Dodson, A.R., Norman, A.R., Dennis, N., Fletcher, A., Southgate, C., Dowe, A., Dearnaley, D., Jhavar, S., Eeles, R., Feber, A., Cooper, C.S. Oncogene (2004) [Pubmed]
  24. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Kleer, C.G., Cao, Q., Varambally, S., Shen, R., Ota, I., Tomlins, S.A., Ghosh, D., Sewalt, R.G., Otte, A.P., Hayes, D.F., Sabel, M.S., Livant, D., Weiss, S.J., Rubin, M.A., Chinnaiyan, A.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  25. Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2. Chen, H., Rossier, C., Antonarakis, S.E. Genomics (1996) [Pubmed]
WikiGenes - Universities