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

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)623-635
Number of pages13
JournalStem Cells
Volume32
Issue number3
DOIs
Publication statusPublished - 01-03-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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    Ye, B., Dai, Z., Liu, B., Wang, R., Li, C., Huang, G., Wang, S., Xia, P., Yang, X., Kuwahara, K., Sakaguchi, N., & Fan, Z. (2014). Pcid2 inactivates developmental genes in human and mouse embryonic stem cells to sustain their pluripotency by modulation of EID1 stability. Stem Cells, 32(3), 623-635. https://doi.org/10.1002/stem.1580