1. Biochemistry and Chemical Biology
  2. Cell Biology
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Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells

  1. Jihoon Shin
  2. Tae Wan Kim
  3. Hyunsoo Kim
  4. Hae Ji Kim
  5. Min Young Suh
  6. Sangho Lee
  7. Han-Teo Lee
  8. Sojung Kwak
  9. Sang-Eun Lee
  10. Jong-Hyuk Lee
  11. Hyonchol Jang
  12. Eun-Jung Cho
  13. Hong-Duk Youn  Is a corresponding author
  1. Seoul National University College of Medicine, Republic of Korea
  2. Seoul National University, Republic of Korea
  3. National Cancer Center, Republic of Korea
  4. Sungkyunkwan University, Republic of Korea
Research Article
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Cite this article as: eLife 2016;5:e10877 doi: 10.7554/eLife.10877

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.

Article and author information

Author details

  1. Jihoon Shin

    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
    Competing interests
    The authors declare that no competing interests exist.
  2. Tae Wan Kim

    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
    Competing interests
    The authors declare that no competing interests exist.
  3. Hyunsoo Kim

    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
    Competing interests
    The authors declare that no competing interests exist.
  4. Hae Ji Kim

    Department of Biological Sciences, Seoul National University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  5. Min Young Suh

    Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  6. Sangho Lee

    Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  7. Han-Teo Lee

    Interdisciplinary Program in Genetic Engineering, Seoul National University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  8. Sojung Kwak

    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
    Competing interests
    The authors declare that no competing interests exist.
  9. Sang-Eun Lee

    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
    Competing interests
    The authors declare that no competing interests exist.
  10. Jong-Hyuk Lee

    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
    Competing interests
    The authors declare that no competing interests exist.
  11. Hyonchol Jang

    Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  12. Eun-Jung Cho

    College of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  13. Hong-Duk Youn

    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
    For correspondence
    hdyoun@snu.ac.kr
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. George Q Daley, Harvard Medical School, United States

Publication history

  1. Received: August 14, 2015
  2. Accepted: February 13, 2016
  3. Accepted Manuscript published: February 15, 2016 (version 1)
  4. Accepted Manuscript updated: February 17, 2016 (version 2)
  5. Version of Record published: March 9, 2016 (version 3)

Copyright

© 2016, Shin et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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