The Polycomb group protein EZH2 directly controls DNA methylation

Nature. 2006 Feb 16;439(7078):871-4. doi: 10.1038/nature04431. Epub 2005 Dec 14.

Abstract

The establishment and maintenance of epigenetic gene silencing is fundamental to cell determination and function. The essential epigenetic systems involved in heritable repression of gene activity are the Polycomb group (PcG) proteins and the DNA methylation systems. Here we show that the corresponding silencing pathways are mechanistically linked. We find that the PcG protein EZH2 (Enhancer of Zeste homolog 2) interacts-within the context of the Polycomb repressive complexes 2 and 3 (PRC2/3)-with DNA methyltransferases (DNMTs) and associates with DNMT activity in vivo. Chromatin immunoprecipitations indicate that binding of DNMTs to several EZH2-repressed genes depends on the presence of EZH2. Furthermore, we show by bisulphite genomic sequencing that EZH2 is required for DNA methylation of EZH2-target promoters. Our results suggest that EZH2 serves as a recruitment platform for DNA methyltransferases, thus highlighting a previously unrecognized direct connection between two key epigenetic repression systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin Immunoprecipitation
  • CpG Islands / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation*
  • DNA-Binding Proteins / classification*
  • DNA-Binding Proteins / metabolism*
  • Enhancer of Zeste Homolog 2 Protein
  • Epigenesis, Genetic
  • Gene Silencing*
  • HeLa Cells
  • Humans
  • Polycomb Repressive Complex 2
  • Polycomb-Group Proteins
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Repressor Proteins / classification*
  • Repressor Proteins / metabolism*
  • Substrate Specificity
  • Transcription Factors / classification*
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Polycomb-Group Proteins
  • Repressor Proteins
  • Transcription Factors
  • DNA (Cytosine-5-)-Methyltransferases
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2