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      Roles of the EZH2 histone methyltransferase in cancer epigenetics.

      1 ,
      Mutation research
      Elsevier BV

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          Abstract

          EZH2 is the catalytic subunit of Polycomb repressive complex 2 (PRC2), which is a highly conserved histone methyltransferase that targets lysine-27 of histone H3. This methylated H3-K27 chromatin mark is commonly associated with silencing of differentiation genes in organisms ranging from plants to flies to humans. Studies on human tumors show that EZH2 is frequently over-expressed in a wide variety of cancerous tissue types, including prostate and breast. Although the mechanistic contributions of EZH2 to cancer progression are not yet determined, functional links between EZH2-mediated histone methylation and DNA methylation suggest partnership with the gene silencing machinery implicated in tumor suppressor loss. Here we review the basic molecular biology of EZH2 and the findings that implicate EZH2 in different cancers. We also discuss EZH2 connections to other silencing enzymes, such as DNA methyltransferases and histone deacetylases, and we consider progress on deciphering mechanistic consequences of EZH2 overabundance and its potential roles in tumorigenesis. Finally, we review recent findings that link EZH2 roles in stem cells and cancer, and we consider prospects for integrating EZH2 blockade into strategies for developing epigenetic therapies.

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          Author and article information

          Journal
          Mutat Res
          Mutation research
          Elsevier BV
          0027-5107
          0027-5107
          Dec 01 2008
          : 647
          : 1-2
          Affiliations
          [1 ] Department of Genetics, University of Minnesota, Minneapolis, MN 55455, USA. simon004@umn.edu
          Article
          S0027-5107(08)00142-5
          10.1016/j.mrfmmm.2008.07.010
          18723033
          f00dea20-18b8-419d-b3f6-7670d21684b4
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