Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells
- Seoul National University College of Medicine, Republic of Korea
- Seoul National University, Republic of Korea
- National Cancer Center, Republic of Korea
- Sungkyunkwan University, Republic of Korea
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.
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Author details
Reviewing Editor
- George Q Daley, Harvard Medical School, United States
Version history
- Received: August 14, 2015
- Accepted: February 13, 2016
- Accepted Manuscript published: February 15, 2016 (version 1)
- Accepted Manuscript updated: February 17, 2016 (version 2)
- 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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Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells
eLife 5:e10877.
https://doi.org/10.7554/eLife.10877
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