Pcid2 inactivates developmental genes in human and mouse embryonic stem cells to sustain their pluripotency by modulation of EID1 stability

Buqing Ye, Zhonghua Dai, Benyu Liu, Rui Wang, Chong Li, Guanling Huang, Shuo Wang, Pengyan Xia, Xuan Yang, Kazuhiko Kuwahara, Nobuo Sakaguchi, Zusen Fan

研究成果: Article査読

12 被引用数 (Scopus)

抄録

Self-renewal and differentiation are the hallmarks of embryonic stem cells (ESCs). However, it is largely unknown about how the pluripotency is regulated. Here we demonstrate that Pcid2 is required for the maintenance of self-renewal both in mouse and human ESCs. Pcid2 plays a critical role in suppression of ESC differentiation. Pcid2 deficiency causes early embryonic lethality before the blastocyst stage. Pcid2 associates with EID1 and is present in the CBP/p300-EID1 complex in the ESCs. We show that MDM2 is an E3 ligase for K48-linked EID1 ubiquitination for its degradation. For the maintenance of self-renewal, Pcid2 binds to EID1 to impede the association with MDM2. Then EID1 is not degraded to sustain its stability to block the HAT activity of CBP/p300, leading to suppression of the developmental gene expression. Collectively, Pcid2 is present in the CBP/p300-EID1 complex to control the switch balance of mouse and human ESCs through modulation of EID1 degradation.

本文言語English
ページ(範囲)623-635
ページ数13
ジャーナルStem Cells
32
3
DOI
出版ステータスPublished - 03-2014
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子医療
  • 発生生物学
  • 細胞生物学

フィンガープリント

「Pcid2 inactivates developmental genes in human and mouse embryonic stem cells to sustain their pluripotency by modulation of EID1 stability」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル