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

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

Author information

1
Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
2
Core Research for Evolutional Science and Technology, Yokohama, Japan.
3
Centre for Translational Medicine,Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
4
International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.
5
Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
6
Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
7
Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
8
Department of Developmental Stem Cell Biology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
9
Department of Biochemistry, Oxford University, Oxford, United Kingdom.
10
Chromosome Engineering Team, Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan.
11
Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
12
Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.

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

PMID:
28304275
PMCID:
PMC5375644
DOI:
10.7554/eLife.21064
[Indexed for MEDLINE]
Free PMC Article

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