文献类型： 外文期刊

作者： Zhao, Wukui ¹ ; Liu, Mengjie ¹ ; Ji, Haijing ³ ; Zhu, Yaru ¹ ; Wang, Congcong ¹ ; Huang, Yikai ¹ ; Ma, Xiaoqi ¹ ; Xing, G ¹ ;

作者机构： 1.Nanjing Univ, Model Anim Res Ctr, State Key Lab Pharmaceut Biotechnol, 12 Xuefu Rd, Nanjing 210032, Jiangsu, Peoples R China

2.Nanjing Univ, Model Anim Res Ctr, MOE Key Lab Model Anim Dis Study, 12 Xuefu Rd, Nanjing 210032, Jiangsu, Peoples R China

3.Nanjing Agr Univ, Coll Anim Sci & Technol, Nanjing 210095, Jiangsu, Peoples R China

4.Jiangsu Acad Agr Sci, Inst Anim Sci, Nanjing 210014, Jiangsu, Peoples R China

5.Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China

6.Nanjing Univ, Med Sch, Nanjing Drum Tower Hosp, Dept Sports Med & Adult Reconstruct Surg, Nanjing 210008, Jiangsu, Peoples R China

关键词： embryonic stem cell; polycomb; phosphorylation; epigenetics; differentiation; H2AK119ub1; PRC1; Yaf2

期刊名称：JOURNAL OF BIOLOGICAL CHEMISTRY （ 影响因子：5.157； 五年影响因子：5.041 ）

ISSN： 0021-9258

年卷期： 2018 年 293 卷 33 期

页码：

收录情况： SCI

摘要： The polycomb group (PcG) proteins are key epigenetic regulators in stem cell maintenance. PcG proteins have been thought to act through one of two polycomb repressive complexes (PRCs), but more recent biochemical analyses have challenged this model in the identification of noncanonical PRC1 (nc-PRC1) complexes characterized by the presence of Rybp or Yaf2 in place of the canonical Chromobox proteins. However, the biological significance of these nc-PRC1s and the potential mechanisms by which they mediate gene repression are largely unknown. Here, we explore the functional consequences of Yaf2 disruption on stem cell regulation. We show that deletion of Yaf2 results in compromised proliferation and abnormal differentiation of mouse embryonic stem cells (mESCs). Genome-wide profiling indicates Yaf2 functions primarily as a transcriptional repressor, particularly impacting genes associated with ectoderm cell fate in a manner distinct from Rybp. We confirm that Yaf2 assembles into a noncanonical PRC complex, with deletion analysis identifying the region encompassing amino acid residues 102-150 as required for this assembly. Furthermore, we identified serine 166 as a Yaf2 phosphorylation site, and we demonstrate that mutation of this site to alanine (S166A) compromises Ring1B-mediated H2A monoubiquitination and in turn its ability to repress target gene expression. We therefore propose that Yaf2 and its phosphorylation status serve as dual regulators to maintain the pluripotent state in mESCs.