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Gene Review

Ezh2  -  enhancer of zeste homolog 2 (Drosophila)

Mus musculus

Synonyms: ENX-1, Enhancer of zeste homolog 2, Enx-1, Enx1h, Histone-lysine N-methyltransferase EZH2, ...
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Disease relevance of Ezh2

  • Ezh2 levels are increasingly elevated during prostate cancer progression [1].
  • We observed that Ezh2 binds to pRb2/p130, a member of the retinoblastoma family; as such, we were led to consider the possible ability of Ezh2 to modulate cell cycle progression [2].

High impact information on Ezh2

  • Revealed function of Ezh2 points to a broader usage of lysine methylation in regulation of both nuclear and extra-nuclear signaling processes [3].
  • Genetic evidence supports the essential role of cytosolic Ezh2 in actin polymerization-dependent processes such as antigen receptor signaling in T cells and PDGF-induced dorsal circular ruffle formation in fibroblasts [3].
  • Eed-Ezh2 Polycomb complexes are recruited to the paternal chromosome and potentially regulate its repressive histone methylation [4].
  • The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation [5].
  • In undifferentiated myoblasts, endogenous Ezh2 was associated with the transcriptional regulator YY1 [5].

Biological context of Ezh2

  • The early lethal phenotype is reminiscent of that of the PcG-gene knockouts Eed and Ezh2, which belong to a separate functional PcG group and PcG protein complex [6].
  • This accumulation and the associated histone methylation are also lost in Ezh2 mutants, suggesting a role in X inactivation [7].
  • By contrast, in the differentiating trophectoderm cells where Oct4 expression is progressively downregulated Ezh2/Eed complex is recruited transiently to one X chromosome in female embryos at the onset of X-inactivation [7].
  • Enhancer of zeste 2 (Ezh2), a SET domain-containing protein, is crucial for development in many model organisms, including early mouse development [7].
  • This phenotypic effect on growth could be attributed to the asymmetric localisation of the Ezh2/Eed complex and the associated histone methylation pattern to the maternal genome, which is disrupted in Ezh2 mutant zygotes [7].

Anatomical context of Ezh2


Associations of Ezh2 with chemical compounds

  • Quiescent B cells also lacked heterochromatin-associated HP1beta and Ikaros at pericentric chromatin and expressed low levels of Ezh2 and ESET histone methyl transferases (HMTases) [11].

Physical interactions of Ezh2

  • The association of Eed/Enx1 complexes is mitotically stable, suggesting a mechanism for the maintenance of imprinted X inactivation in these cells [9].

Regulatory relationships of Ezh2


Other interactions of Ezh2

  • Therefore, STAT5 functions at a distinct step in regulating distal V(H) recombination in relation to the transcription factor Pax5 and histone methyltransferase Ezh2 [12].
  • Here we show that Eed and a second Polycomb group protein, Enx1, are directly localized to the inactive X chromosome in XX trophoblast stem (TS) cells [9].
  • The murine polycomb-group genes Ezh1 and Ezh2 map close to Hox gene clusters on mouse chromosomes 11 and 6 [13].
  • Our data suggest Ezh2-dependent histone H3 methylation as a novel regulatory mechanism controlling Igh rearrangement during early murine B cell development [10].
  • The expression profile of the newly produced CD41+ cells showed high levels of transcripts encoding Ezh2, TdT, Rag2, and various immunoglobulin (Ig) heavy chains [14].

Analytical, diagnostic and therapeutic context of Ezh2

  • More importantly, whereas normal HSCs were rapidly exhausted after serial transplantations, overexpression of Ezh2 completely conserved long-term repopulating potential [15].


  1. Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation. Kuzmichev, A., Margueron, R., Vaquero, A., Preissner, T.S., Scher, M., Kirmizis, A., Ouyang, X., Brockdorff, N., Abate-Shen, C., Farnham, P., Reinberg, D. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  2. Ezh2 reduces the ability of HDAC1-dependent pRb2/p130 transcriptional repression of cyclin A. Tonini, T., Bagella, L., D'Andrilli, G., Claudio, P.P., Giordano, A. Oncogene (2004) [Pubmed]
  3. Polycomb group protein ezh2 controls actin polymerization and cell signaling. Su, I.H., Dobenecker, M.W., Dickinson, E., Oser, M., Basavaraj, A., Marqueron, R., Viale, A., Reinberg, D., Wülfing, C., Tarakhovsky, A. Cell (2005) [Pubmed]
  4. Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes. Umlauf, D., Goto, Y., Cao, R., Cerqueira, F., Wagschal, A., Zhang, Y., Feil, R. Nat. Genet. (2004) [Pubmed]
  5. The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation. Caretti, G., Di Padova, M., Micales, B., Lyons, G.E., Sartorelli, V. Genes Dev. (2004) [Pubmed]
  6. Rnf2 (Ring1b) deficiency causes gastrulation arrest and cell cycle inhibition. Voncken, J.W., Roelen, B.A., Roefs, M., de Vries, S., Verhoeven, E., Marino, S., Deschamps, J., van Lohuizen, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  7. Consequences of the depletion of zygotic and embryonic enhancer of zeste 2 during preimplantation mouse development. Erhardt, S., Su, I.H., Schneider, R., Barton, S., Bannister, A.J., Perez-Burgos, L., Jenuwein, T., Kouzarides, T., Tarakhovsky, A., Surani, M.A. Development (2003) [Pubmed]
  8. Developmental regulation of Suz 12 localization. de la Cruz, C.C., Fang, J., Plath, K., Worringer, K.A., Nusinow, D.A., Zhang, Y., Panning, B. Chromosoma (2005) [Pubmed]
  9. Mitotically stable association of polycomb group proteins eed and enx1 with the inactive x chromosome in trophoblast stem cells. Mak, W., Baxter, J., Silva, J., Newall, A.E., Otte, A.P., Brockdorff, N. Curr. Biol. (2002) [Pubmed]
  10. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Su, I.H., Basavaraj, A., Krutchinsky, A.N., Hobert, O., Ullrich, A., Chait, B.T., Tarakhovsky, A. Nat. Immunol. (2003) [Pubmed]
  11. Histone hypomethylation is an indicator of epigenetic plasticity in quiescent lymphocytes. Baxter, J., Sauer, S., Peters, A., John, R., Williams, R., Caparros, M.L., Arney, K., Otte, A., Jenuwein, T., Merkenschlager, M., Fisher, A.G. EMBO J. (2004) [Pubmed]
  12. Regulation of interleukin 7-dependent immunoglobulin heavy-chain variable gene rearrangements by transcription factor STAT5. Bertolino, E., Reddy, K., Medina, K.L., Parganas, E., Ihle, J., Singh, H. Nat. Immunol. (2005) [Pubmed]
  13. The murine polycomb-group genes Ezh1 and Ezh2 map close to Hox gene clusters on mouse chromosomes 11 and 6. Laible, G., Haynes, A.R., Lebersorger, A., O'Carroll, D., Mattei, M.G., Denny, P., Brown, S.D., Jenuwein, T. Mamm. Genome (1999) [Pubmed]
  14. Novel pathway for megakaryocyte production after in vivo conditional eradication of integrin alphaIIb-expressing cells. Jacquelin, B., Kortulewski, T., Vaigot, P., Pawlik, A., Gruel, G., Alibert, O., Soularue, P., Joubert, C., Gidrol, X., Tronik-Le Roux, D. Blood (2005) [Pubmed]
  15. The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Kamminga, L.M., Bystrykh, L.V., de Boer, A., Houwer, S., Douma, J., Weersing, E., Dontje, B., de Haan, G. Blood (2006) [Pubmed]
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