title: Pcid2 inactivates developmental genes in human and mouse embryonic stem cells to sustain their pluripotency by modulation of EID1 stability.
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.
authors.affiliation: Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Buqing
authors.initials: B
authors.lastname: Ye
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Dai
authors.forename: Benyu
authors.initials: B
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.forename: Guanling
authors.initials: G
authors.lastname: Huang
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.forename: Pengyan
authors.initials: P
authors.lastname: Xia
authors.forename: Xuan
authors.initials: X
authors.lastname: Yang
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kuwahara
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakaguchi
authors.forename: Zusen
authors.initials: Z
authors.lastname: Fan
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008239:Lysine / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D059748:Proteolysis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C416925:EID1 protein, human; C000592215:EID1 protein, mouse; D009687:Nuclear Proteins; C586854:PCID2 protein, human; C000592213:PCID2 protein, mouse; D012097:Repressor Proteins; D050880:p300-CBP Transcription Factors; D051736:Proto-Oncogene Proteins c-mdm2; D044767:Ubiquitin-Protein Ligases; D008239:Lysine
keywords: E1A-like inhibitor of differentiation 1 ubiquitination; Embryonic stem cells; MDM2; PCI-domain containing protein 2; Pluripotency