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

eLife

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

关键词: epigenetics;    germ cells;    embryonic stem cells;    cell differentiation;    transcription factors;    Polycomb;    Mouse;   

DOI  :  10.7554/eLife.21064

来源: publisher

【 摘 要 】

10.7554/eLife.21064.001The 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.DOI: http://dx.doi.org/10.7554/eLife.21064.001

【 授权许可】

CC BY