PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes

Elife. 2017 Mar 17;6:e21064. doi: 10.7554/eLife.21064.

Abstract

The ring finger protein PCGF6 (polycomb group ring finger 6) interacts with RING1A/B and E2F6 associated factors to form a non-canonical PRC1 (polycomb repressive complex 1) known as PCGF6-PRC1. Here, we demonstrate that PCGF6-PRC1 plays a role in repressing a subset of PRC1 target genes by recruiting RING1B and mediating downstream mono-ubiquitination of histone H2A. PCGF6-PRC1 bound loci are highly enriched for promoters of germ cell-related genes in mouse embryonic stem cells (ESCs). Conditional ablation of Pcgf6 in ESCs leads to robust de-repression of such germ cell-related genes, in turn affecting cell growth and viability. We also find a role for PCGF6 in pre- and peri-implantation mouse embryonic development. We further show that a heterodimer of the transcription factors MAX and MGA recruits PCGF6 to target loci. PCGF6 thus links sequence specific target recognition by the MAX/MGA complex to PRC1-dependent transcriptional silencing of germ cell-specific genes in pluripotent stem cells.

Keywords: Polycomb; cell biology; cell differentiation; developmental biology; embryonic stem cells; epigenetics; germ cells; mouse; stem cells; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Embryonic Stem Cells / physiology*
  • Gene Expression Regulation*
  • Gene Silencing
  • Histones / metabolism
  • Mice
  • Polycomb Repressive Complex 1 / metabolism*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Histones
  • Pcgf6 protein, mouse
  • Polycomb Repressive Complex 1
  • Rnf2 protein, mouse
  • Ubiquitin-Protein Ligases

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.