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Publication : Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells.

First Author  Shin J Year  2016
Journal  Elife Volume  5
Pages  e10877 PubMed ID  26880562
Mgi Jnum  J:231011 Mgi Id  MGI:5766666
Doi  10.7554/eLife.10877 Citation  Shin J, et al. (2016) Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells. Elife 5:e10877
abstractText  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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