title: Oct4 resetting by Aurkb-PP1 cell cycle axis determines the identity of mouse embryonic stem cells.
abstract: In embryonic stem cells (ESCs), cell cycle regulation is deeply connected to pluripotency. Especially, core transcription factors (CTFs) which are essential to maintaining the pluripotency transcription programs should be reset during M/G1 transition. However, it remains unknown about how CTFs are governed during cell cycle progression. Here, we describe that the regulation of Oct4 by Aurora kinase b (Aurkb)/protein phosphatase 1 (PP1) axis during the cell cycle is important for resetting Oct4 to pluripotency and cell cycle related target genes in determining the identity of ESCs. Aurkb starts to phosphorylate Oct4(S229) at the onset of G2/M phase, inducing the dissociation of Oct4 from chromatin, whereas PP1 binds Oct4 and dephosphorylates Oct4(S229) during M/G1 transition, which resets Oct4-driven transcription for pluripotency and the cell cycle. Furthermore, Aurkb phosphormimetic and PP1 binding-deficient mutations in Oct4 disrupt the pluripotent cell cycle, lead to the loss of pluripotency in ESCs, and decrease the efficiency of somatic cell reprogramming. Based on our findings, we suggest that the cell cycle is directly linked to pluripotency programs in ESCs. [BMB Reports 2016; 49(10): 527-528].
authors.affiliation: National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic and Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 08826, Korea.
authors.forename: Jihoon
authors.initials: J
authors.lastname: Shin
authors.affiliation: National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic and Hypoxic Disease Institute, Seoul National University College of Medicine; Department of Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul 08826, Korea.
authors.forename: Hong-Duk
authors.initials: HD
authors.lastname: Youn
mesh_terms: D000818:Animals; D064107:Aurora Kinase B / Q000378:metabolism*; D065150:Cellular Reprogramming; D002843:Chromatin / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints; D059566:M Phase Cell Cycle Checkpoints; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000378:metabolism*
chemical_list: D002843:Chromatin; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D064107:Aurora Kinase B; D054645:Protein Phosphatase 1