The polycomb group protein Yaf2 regulates the pluripotency of embryonic stem cells in a phosphorylation-dependent manner
The polycomb group protein Yaf2 regulates the pluripotency of embryonic stem cells in a phosphorylation-dependent manner
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多梳蛋白Yaf2以磷酸化依赖性方式调节胚胎干细胞的多能性
DOI：
10.1074/jbc.ra118.003299
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
J. Qin
中科院分区：
文献类型：
--
作者：
Wukui Zhao;Mengjie Liu;Haijing Ji;Yaru Zhu;Congcong Wang;Yikai Huang;Xiaoqi Ma;Guangdong Xing;Yin Xia;Q. Jiang;J. Qin
polycomb group （PcG）蛋白是干细胞维持过程中关键的表观遗传调控因子。PcG蛋白被认为是通过两种多梳抑制复合物（PRCs）中的一种起作用，但最近的生化分析在鉴定非规范PRC1 （nc-PRC1）复合物时对这一模型提出了挑战，其特征是Rybp或Yaf2取代了规范的Chromobox蛋白。然而，这些nc-PRC1s的生物学意义及其介导基因抑制的潜在机制在很大程度上是未知的。在这里，我们探讨了Yaf2破坏对干细胞调控的功能后果。我们发现Yaf2的缺失导致小鼠胚胎干细胞（mESCs）增殖受损和异常分化。全基因组分析表明，Yaf2主要作为转录抑制因子发挥作用，特别是以与Rybp不同的方式影响与外胚层细胞命运相关的基因。我们确认Yaf2组装成一个非规范的PRC复合体，通过缺失分析确定了包含该组装所需的氨基酸残基102-150的区域。此外，我们发现丝氨酸166是Yaf2的磷酸化位点，并证明该位点突变为丙氨酸（S166A）会损害环1b介导的H2A单泛素化，进而抑制靶基因表达的能力。因此，我们认为Yaf2及其磷酸化状态可以作为双重调节因子来维持mESCs的多能状态。
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.
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影响因子：
23.9
作者：
Qin, Jinzhong;Whyte, Warren A.;Anderssen, Endre;Apostolou, Effie;Chen, Hsu-Hsin;Akbarian, Schahram;Bronson, Roderick T.;Hochedlinger, Konrad;Ramaswamy, Sridhar;Young, Richard A.;Hock, Hanno
通讯作者：
Hock, Hanno
DOI：
10.1016/j.str.2010.04.013
发表时间：
2010-08-11
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Wang R;Taylor AB;Leal BZ;Chadwell LV;Ilangovan U;Robinson AK;Schirf V;Hart PJ;Lafer EM;Demeler B;Hinck AP;McEwen DG;Kim CA
通讯作者：
Kim CA
影响因子：
16
作者：
Cao, R;Tsukada, Y;Zhang, Y
通讯作者：
Zhang, Y
影响因子：
10.5
作者：
Srinivasan, L;Atchison, ML
通讯作者：
Atchison, ML
影响因子：
16
作者：
Trojer P;Cao AR;Gao Z;Li Y;Zhang J;Xu X;Li G;Losson R;Erdjument-Bromage H;Tempst P;Farnham PJ;Reinberg D
通讯作者：
Reinberg D