title: Role of nuclear receptor coactivator 3 (Ncoa3) in pluripotency maintenance.
abstract: Nuclear receptors, including Esrrb, Dax1, and Nr5a2, have been shown to be involved in pluripotency maintenance. Yet, the role of their coactivators in mouse embryonic stem cells remains unexplored. Here, we demonstrated that the nuclear receptor coactivator 3 (Ncoa3) is essential for pluripotency maintenance. Knockdown of Ncoa3 not only compromises the expression of pluripotency markers but also impairs in vitro and in vivo differentiation potential of mouse ESCs. Ncoa3 binds to the Nanog promoter and recruits the histone acetyltransferase CREB binding protein (CBP) and the histone arginine methyltransferase CARM1 to activate Nanog expression. Moreover, glycogen synthase kinase 3 GSK3 signaling down-regulates the Ncoa3 protein level to suppress Nanog expression. Thus, Ncoa3 not only contributes to self-renewal by activating Nanog but also facilitates ESC differentiation as a break point to disrupt the core transcriptional circuitry of pluripotency.
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics and College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Zhaoting
authors.initials: Z
authors.lastname: Wu
authors.forename: Meng
authors.initials: M
authors.lastname: Yang
authors.forename: Hongjie
authors.initials: H
authors.lastname: Liu
authors.forename: Hongchao
authors.initials: H
authors.lastname: Guo
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Cheng
authors.forename: Lingyi
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D000071317:Nanog Homeobox Protein; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1; D050882:CREB-Binding Protein; C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3; D038362:Glycogen Synthase Kinase 3