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

• Published in: eLife Vol. 6
• Main Authors: Endoh, Mitsuhiro, Endo, Takaho A, Shinga, Jun, Hayashi, Katsuhiko, Farcas, Anca, Ma, Kit-Wan, Ito, Shinsuke, Sharif, Jafar, Endoh, Tamie, Onaga, Naoko, Nakayama, Manabu, Ishikura, Tomoyuki, Masui, Osamu, Kessler, Benedikt M, Suda, Toshio, Ohara, Osamu, Okuda, Akihiko, Klose, Robert, Koseki, Haruhiko
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 17-03-2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Ablation; Animals; Biology; Cell Biology; Cell Differentiation; Deoxyribonucleic acid; Developmental Biology and Stem Cells; DNA; DNA methylation; Embryo cells; Embryogenesis; Embryonic stem cells; Embryonic Stem Cells - physiology; Epigenetics; Gene expression; Gene Expression Regulation; Gene Silencing; Genes; Genetic aspects; Genomics; germ cells; Histone H2A; Histones - metabolism; Kinases; Laboratories; Medicine; Metalloproteins; Mice; Observations; Physiological aspects; Pluripotency; Polycomb; Polycomb group proteins; Polycomb Repressive Complex 1 - metabolism; Proteins; Stem cell transplantation; Stem cells; Transcription factors; Ubiquitin-Protein Ligases - metabolism; Ubiquitination; mouse; stem cells; cell differentiation; cell biology; transcription factors; developmental biology; embryonic stem cells; Polycomb; germ cells; epigenetics
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.21064

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
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.