title: Loss of Polycomb Group Protein Pcgf1 Severely Compromises Proper Differentiation of Embryonic Stem Cells.
abstract: The Polycomb repressive complex 1 (PRC1) is essential for fate decisions of embryonic stem (ES) cells. Emerging evidence suggests that six major variants of PRC1 complex, defined by the mutually exclusive presence of Pcgf subunit, regulate distinct biological processes, yet very little is known about the mechanism by which each version of PRC1 instructs and maintains cell fate. Here, we disrupted the Pcgf1, also known as Nspc1 and one of six Pcgf paralogs, in mouse ES cells by the CRISPR/Cas9 technology. We showed that although these mutant cells were viable and retained normal self-renewal, they displayed severe defects in differentiation in vitro. To gain a better understanding of the role of Pcgf1 in transcriptional control of differentiation, we analysed mRNA profiles from Pcgf1 deficient cells using RNA-seq. Interestingly, we found that Pcgf1 positively regulated expression of essential transcription factors involved in ectoderm and mesoderm differentiation, revealing an unexpected function of Pcgf1 in gene activation during ES cell lineage specification. Chromatin immunoprecipitation experiments demonstrated that Pcgf1 deletion caused a decrease in Ring1B and its associated H2AK119ub1 mark binding to target genes. Altogether, our results suggested an unexpected function of Pcgf1 in gene activation during ES cell maintenance.
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yan
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China.
authors.forename: Wukui
authors.initials: W
authors.lastname: Zhao
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China.
authors.forename: Yikai
authors.initials: Y
authors.lastname: Huang
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Tong
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Qin
mesh_terms: D000818:Animals; D015415:Biomarkers; D064113:CRISPR-Cas Systems; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D000066673:Cell Self Renewal / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D055786:Gene Knockout Techniques; D018390:Gene Targeting; D051379:Mice; D008954:Models, Biological; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000172:deficiency*; D011485:Protein Binding; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D015415:Biomarkers; C570527:Pcgf1 protein, mouse; D015534:Trans-Activators; D063150:Polycomb Repressive Complex 1