The histone H3 lysine 9 methyltransferases G9a and GLP regulate polycomb repressive complex 2-mediated gene silencing

Mol Cell. 2014 Jan 23;53(2):277-89. doi: 10.1016/j.molcel.2013.12.005. Epub 2014 Jan 2.


G9a/GLP and Polycomb Repressive Complex 2 (PRC2) are two major epigenetic silencing machineries, which in particular methylate histone H3 on lysines 9 and 27 (H3K9 and H3K27), respectively. Although evidence of a crosstalk between H3K9 and H3K27 methylations has started to emerge, their actual interplay remains elusive. Here, we show that PRC2 and G9a/GLP interact physically and functionally. Moreover, combining different genome-wide approaches, we demonstrate that Ezh2 and G9a/GLP share an important number of common genomic targets, encoding developmental and neuronal regulators. Furthermore, we show that G9a enzymatic activity modulates PRC2 genomic recruitment to a subset of its target genes. Taken together, our findings demonstrate an unanticipated interplay between two main histone lysine methylation mechanisms, which cooperate to maintain silencing of a subset of developmental genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enhancer of Zeste Homolog 2 Protein
  • Gene Expression Regulation
  • Gene Silencing*
  • HeLa Cells
  • Histocompatibility Antigens / metabolism
  • Histocompatibility Antigens / physiology*
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histone-Lysine N-Methyltransferase / physiology*
  • Histones / metabolism*
  • Humans
  • Methylation
  • Polycomb Repressive Complex 2 / physiology*
  • Promoter Regions, Genetic


  • Histocompatibility Antigens
  • Histones
  • EHMT1 protein, human
  • EHMT2 protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Histone-Lysine N-Methyltransferase
  • Polycomb Repressive Complex 2

Associated data

  • GEO/GSE46545