eLife (Mar 2017)

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

  • Mitsuhiro Endoh,
  • Takaho A Endo,
  • Jun Shinga,
  • Katsuhiko Hayashi,
  • Anca Farcas,
  • Kit-Wan Ma,
  • Shinsuke Ito,
  • Jafar Sharif,
  • Tamie Endoh,
  • Naoko Onaga,
  • Manabu Nakayama,
  • Tomoyuki Ishikura,
  • Osamu Masui,
  • Benedikt M Kessler,
  • Toshio Suda,
  • Osamu Ohara,
  • Akihiko Okuda,
  • Robert Klose,
  • Haruhiko Koseki

DOI
https://doi.org/10.7554/eLife.21064
Journal volume & issue
Vol. 6

Abstract

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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.

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