title: Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells.
abstract: Pluripotency transcription programs by core transcription factors (CTFs) might be reset during M/G1 transition to maintain the pluripotency of embryonic stem cells (ESCs). However, little is known about how CTFs are governed during cell cycle progression. Here, we demonstrate that the regulation of Oct4 by Aurora kinase b (Aurkb)/protein phosphatase 1 (PP1) during the cell cycle is important for resetting Oct4 to pluripotency and cell cycle genes in determining the identity of ESCs. Aurkb phosphorylates Oct4(S229) during G2/M phase, leading to 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. Aurkb phosphor-mimetic and PP1 binding-deficient mutations in Oct4 alter the cell cycle, effect the loss of pluripotency in ESCs, and decrease the efficiency of somatic cell reprogramming. Our findings provide evidence that the cell cycle is linked directly to pluripotency programs in ESCs.
authors.affiliation: National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of 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/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Tae Wan
authors.initials: TW
authors.lastname: Kim
authors.affiliation: National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyunsoo
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hye Ji
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul, Republic of Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Suh
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sangho
authors.initials: S
authors.lastname: Lee
authors.affiliation: Interdisciplinary Program in Genetic Engineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Han-Teo
authors.initials: HT
authors.lastname: Lee
authors.affiliation: National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sojung
authors.initials: S
authors.lastname: Kwak
authors.affiliation: National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Sang-Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jong-Hyuk
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Republic of Korea.
authors.forename: Hyonchol
authors.identifier: http://orcid.org/0000-0003-1436-457X
authors.initials: H
authors.lastname: Jang
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Cho
authors.affiliation: National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul, Republic of Korea.|Interdisciplinary Program in Genetic Engineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hong-Duk
authors.identifier: http://orcid.org/0000-0001-9741-8566
authors.initials: HD
authors.lastname: Youn
mesh_terms: D000818:Animals; D064107:Aurora Kinase B / Q000378:metabolism*; D002453:Cell Cycle; D053595:Embryonic Stem Cells / Q000502:physiology*; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
chemical_list: D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; C517103:Ppp1cc protein, mouse; D054645:Protein Phosphatase 1
keywords: PP1; aurkb; biochemistry; cell biology; cell cycle of ESCs; mouse; oct4 phosphorylation; oct4 resetting