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

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

eLife (2017-03-18)
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
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.

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