title: Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity.
abstract: The Polycomb group (PcG) proteins mediate heritable silencing of developmental regulators in metazoans, participating in one of two distinct multimeric protein complexes, the Polycomb repressive complexes 1 (PRC1) and 2 (PRC2). Although PRC2 has been shown to share target genes with the core transcription network, including Oct3/4, to maintain embryonic stem (ES) cells, it is still unclear whether PcG proteins and the core transcription network are functionally linked. Here, we identify an essential role for the core PRC1 components Ring1A/B in repressing developmental regulators in mouse ES cells and, thereby, in maintaining ES cell identity. A significant proportion of the PRC1 target genes are also repressed by Oct3/4. We demonstrate that engagement of PRC1 at target genes is Oct3/4-dependent, whereas engagement of Oct3/4 is PRC1-independent. Moreover, upon differentiation induced by Gata6 expression, most of the Ring1A/B target genes are derepressed and the binding of Ring1A/B to their target loci is also decreased. Collectively, these results indicate that Ring1A/B-mediated Polycomb silencing functions downstream of the core transcriptional regulatory circuitry to maintain ES cell identity.
authors.affiliation: RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Endoh
authors.forename: Takaho A
authors.initials: TA
authors.lastname: Endo
authors.forename: Tamie
authors.initials: T
authors.lastname: Endoh
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Toyoda
authors.forename: Arie P
authors.initials: AP
authors.lastname: Otte
authors.forename: Masaki
authors.initials: M
authors.lastname: Okano
authors.forename: Neil
authors.initials: N
authors.lastname: Brockdorff
authors.forename: Miguel
authors.initials: M
authors.lastname: Vidal
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases; D000099254:Organic Cation Transporter 3
chemical_list: D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; D050814:Octamer Transcription Factor-3; D027701:Organic Cation Transport Proteins; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D044767:Ubiquitin-Protein Ligases; D000099254:Organic Cation Transporter 3; C494760:Gata6 protein, mouse; C494174:Pou5f1 protein, mouse; C489840:Ring1 protein, mouse; C489842:Rnf2 protein, mouse