title: Polycomb Group Protein Pcgf6 Acts as a Master Regulator to Maintain Embryonic Stem Cell Identity.
abstract: The polycomb repressive complex 1 (PRC1) is a multi-subunit complex that plays critical roles in the epigenetic modulation of gene expression. Here, we show that the PRC1 component polycomb group ring finger 6 (Pcgf6) is required to maintain embryonic stem cell (ESC) identity. In contrast to canonical PRC1, Pcgf6 acts as a positive regulator of transcription and binds predominantly to promoters bearing active chromatin marks. Pcgf6 is expressed at high levels in ESCs, and knockdown reduces the expression of the core ESC regulators Oct4, Sox2, and Nanog. Conversely, Pcgf6 overexpression prevents downregulation of these factors and impairs differentiation. In addition, Pcgf6 enhanced reprogramming in both mouse and human somatic cells. The genomic binding profile of Pcgf6 is highly similar to that of trithorax group proteins, but not of PRC1 or PRC2 complexes, suggesting that Pcgf6 functions atypically in ESCs. Our data reveal novel roles for Pcgf6 in directly regulating Oct4, Nanog, Sox2, and Lin28 expression to maintain ESC identity.
authors.affiliation: Department of Pediatrics, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, California, 92093, USA.
authors.forename: Chao-Shun
authors.initials: CS
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, California, 92093, USA.
authors.forename: Kung-Yen
authors.initials: KY
authors.lastname: Chang
authors.affiliation: Department of Bioengineering, University of California San Diego, La Jolla, California, 92093, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Dang
authors.affiliation: Department of Pediatrics, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, California, 92093, USA.|Institute for Genomic Medicine and Moores Cancer Center, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California, 92093, USA.
authors.forename: Tariq M
authors.initials: TM
authors.lastname: Rana
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D046228:Microarray Analysis; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013724:Teratoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D002843:Chromatin; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489428:Myc protein, mouse; D050814:Octamer Transcription Factor-3; C066476:Pcgf6 protein, mouse; C494174:Pou5f1 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D063150:Polycomb Repressive Complex 1