Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/10877 |
| _version_ | 1811181022175297536 |
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| author | Jihoon Shin Tae Wan Kim Hyunsoo Kim Hye Ji Kim Min Young Suh Sangho Lee Han-Teo Lee Sojung Kwak Sang-Eun Lee Jong-Hyuk Lee Hyonchol Jang Eun-Jung Cho Hong-Duk Youn |
| author_facet | Jihoon Shin Tae Wan Kim Hyunsoo Kim Hye Ji Kim Min Young Suh Sangho Lee Han-Teo Lee Sojung Kwak Sang-Eun Lee Jong-Hyuk Lee Hyonchol Jang Eun-Jung Cho Hong-Duk Youn |
| author_sort | Jihoon Shin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:12:25Z |
| format | Article |
| id | doaj.art-317106b2c225460c85aa595686187191 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:12:25Z |
| publishDate | 2016-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-317106b2c225460c85aa5956861871912022-12-22T04:32:28ZengeLife Sciences Publications LtdeLife2050-084X2016-02-01510.7554/eLife.10877Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cellsJihoon Shin0Tae Wan Kim1Hyunsoo Kim2Hye Ji Kim3Min Young Suh4Sangho Lee5Han-Teo Lee6Sojung Kwak7Sang-Eun Lee8Jong-Hyuk Lee9Hyonchol Jang10https://orcid.org/0000-0003-1436-457XEun-Jung Cho11Hong-Duk Youn12https://orcid.org/0000-0001-9741-8566National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of KoreaNational Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of KoreaNational Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Biological Sciences, Seoul National University, Seoul, Republic of KoreaDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul, Republic of KoreaDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul, Republic of KoreaInterdisciplinary Program in Genetic Engineering, Seoul National University, Seoul, Republic of KoreaNational Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of KoreaNational 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 KoreaNational Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of KoreaDivision of Cancer Biology, Research Institute, National Cancer Center, Goyang, Republic of KoreaCollege of Pharmacy, Sungkyunkwan University, Suwon, Republic of KoreaNational 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 KoreaPluripotency 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.https://elifesciences.org/articles/10877aurkbcell cycle of ESCsoct4 phosphorylationoct4 resettingPP1 |
| spellingShingle | Jihoon Shin Tae Wan Kim Hyunsoo Kim Hye Ji Kim Min Young Suh Sangho Lee Han-Teo Lee Sojung Kwak Sang-Eun Lee Jong-Hyuk Lee Hyonchol Jang Eun-Jung Cho Hong-Duk Youn Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells eLife aurkb cell cycle of ESCs oct4 phosphorylation oct4 resetting PP1 |
| title | Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells |
| title_full | Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells |
| title_fullStr | Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells |
| title_full_unstemmed | Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells |
| title_short | Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells |
| title_sort | aurkb pp1 mediated resetting of oct4 during the cell cycle determines the identity of embryonic stem cells |
| topic | aurkb cell cycle of ESCs oct4 phosphorylation oct4 resetting PP1 |
| url | https://elifesciences.org/articles/10877 |
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