title: PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes.
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 ofPcgf6in 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.
authors.affiliation: 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.
authors.forename: Mitsuhiro
authors.identifier: http://orcid.org/0000-0003-0715-1701
authors.initials: M
authors.lastname: Endoh
authors.affiliation: Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Takaho A
authors.initials: TA
authors.lastname: Endo
authors.affiliation: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shinga
authors.affiliation: Department of Developmental Stem Cell Biology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Biochemistry, Oxford University, Oxford, United Kingdom.
authors.forename: Anca
authors.initials: A
authors.lastname: Farcas
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Kit-Wan
authors.initials: KW
authors.lastname: Ma
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.|Core Research for Evolutional Science and Technology, Yokohama, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Ito
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.|Core Research for Evolutional Science and Technology, Yokohama, Japan.
authors.forename: Jafar
authors.initials: J
authors.lastname: Sharif
authors.affiliation: 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.
authors.forename: Tamie
authors.initials: T
authors.lastname: Endoh
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Onaga
authors.affiliation: Chromosome Engineering Team, Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ishikura
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Masui
authors.affiliation: Mass Spectrometry Laboratory, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Benedikt M
authors.initials: BM
authors.lastname: Kessler
authors.affiliation: 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.
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
authors.affiliation: 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.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.affiliation: Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Akihiko
authors.identifier: http://orcid.org/0000-0002-5298-5564
authors.initials: A
authors.lastname: Okuda
authors.affiliation: Department of Biochemistry, Oxford University, Oxford, United Kingdom.
authors.forename: Robert
authors.identifier: http://orcid.org/0000-0002-8726-7888
authors.initials: R
authors.lastname: Klose
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.|Core Research for Evolutional Science and Technology, Yokohama, Japan.
authors.forename: Haruhiko
authors.identifier: http://orcid.org/0000-0001-8424-5854
authors.initials: H
authors.lastname: Koseki
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000502:physiology*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D051379:Mice; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D006657:Histones; C066476:Pcgf6 protein, mouse; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Polycomb; cell biology; cell differentiation; developmental biology; embryonic stem cells; epigenetics; germ cells; mouse; stem cells; transcription factors