title: Essential Role for Polycomb Group Protein Pcgf6 in Embryonic Stem Cell Maintenance and a Noncanonical Polycomb Repressive Complex 1 (PRC1) Integrity.
abstract: The Polycomb group (PcG) proteins have an important role in controlling the expression of key genes implicated in embryonic development, differentiation, and decision of cell fates. Emerging evidence suggests that Polycomb repressive complexes 1 (PRC1) is defined by the six Polycomb group RING finger protein (Pcgf) paralogs, and Pcgf proteins can assemble into noncanonical PRC1 complexes. However, little is known about the precise mechanisms of differently composed noncanonical PRC1 in the maintenance of the pluripotent cell state. Here we disrupt the Pcgf genes in mouse embryonic stem cells by CRISPR-Cas9 and find Pcgf6 null embryonic stem cells display severe defects in self-renewal and differentiation. Furthermore, Pcgf6 regulates genes mostly involved in differentiation and spermatogenesis by assembling a noncanonical PRC1 complex PRC1.6. Notably, Pcgf6 deletion causes a dramatic decrease in PRC1.6 binding to target genes and no loss of H2AK119ub1. Thus, Pcgf6 is essential for recruitment of PRC1.6 to chromatin. Our results reveal a previously uncharacterized, H2AK119ub1-independent chromatin assembly associated with PRC1.6 complex.
authors.affiliation: From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
authors.forename: Wukui
authors.initials: W
authors.lastname: Zhao
authors.affiliation: From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Tong
authors.affiliation: From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
authors.forename: Yikai
authors.initials: Y
authors.lastname: Huang
authors.affiliation: From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yan
authors.affiliation: From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
authors.forename: Huajian
authors.initials: H
authors.lastname: Teng
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China, and.
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 210008, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: From the MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China, qinjz@nicemice.cn.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Qin
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D053595:Embryonic Stem Cells / Q000166:cytology*; D051379:Mice; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000502:physiology*; D063146:Polycomb-Group Proteins / Q000378:metabolism*
chemical_list: C066476:Pcgf6 protein, mouse; D063146:Polycomb-Group Proteins; D063150:Polycomb Repressive Complex 1
keywords: Polycomb; chromatin; embryonic stem cell; epigenetics; transcription regulation