MTF2 Recruits Polycomb Repressive Complex 2 by Helical-Shape-Selective DNA Binding

Nat Genet. 2018 Jul;50(7):1002-1010. doi: 10.1038/s41588-018-0134-8. Epub 2018 May 28.

Abstract

Polycomb-mediated repression of gene expression is essential for development, with a pivotal role played by trimethylation of histone H3 lysine 27 (H3K27me3), which is deposited by Polycomb Repressive Complex 2 (PRC2). The mechanism by which PRC2 is recruited to target genes has remained largely elusive, particularly in vertebrates. Here we demonstrate that MTF2, one of the three vertebrate homologs of Drosophila melanogaster Polycomblike, is a DNA-binding, methylation-sensitive PRC2 recruiter in mouse embryonic stem cells. MTF2 directly binds to DNA and is essential for recruitment of PRC2 both in vitro and in vivo. Genome-wide recruitment of the PRC2 catalytic subunit EZH2 is abrogated in Mtf2 knockout cells, resulting in greatly reduced H3K27me3 deposition. MTF2 selectively binds regions with a high density of unmethylated CpGs in a context of reduced helix twist, which distinguishes target from non-target CpG islands. These results demonstrate instructive recruitment of PRC2 to genomic targets by MTF2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • CpG Islands
  • DNA / genetics*
  • Drosophila Proteins / genetics
  • Drosophila melanogaster / genetics
  • Gene Expression Regulation, Developmental
  • Histones / genetics
  • Methylation
  • Mice
  • Mouse Embryonic Stem Cells / physiology
  • Polycomb Repressive Complex 2 / genetics*
  • Polycomb-Group Proteins
  • Protein Binding

Substances

  • Drosophila Proteins
  • Histones
  • Mtf2 protein, mouse
  • Polycomb-Group Proteins
  • DNA
  • Polycomb Repressive Complex 2