Shin Jihoon, Youn Hong-Duk
National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic and Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 08826, Korea.
National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic and Hypoxic Disease Institute, Seoul National University College of Medicine; Department of Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul 08826, Korea.
BMB Rep. 2016 Oct;49(10):527-528. doi: 10.5483/bmbrep.2016.49.10.161.
In embryonic stem cells (ESCs), cell cycle regulation is deeply connected to pluripotency. Especially, core transcription factors (CTFs) which are essential to maintaining the pluripotency transcription programs should be reset during M/G1 transition. However, it remains unknown about how CTFs are governed during cell cycle progression. Here, we describe that the regulation of Oct4 by Aurora kinase b (Aurkb)/protein phosphatase 1 (PP1) axis during the cell cycle is important for resetting Oct4 to pluripotency and cell cycle related target genes in determining the identity of ESCs. Aurkb starts to phosphorylate Oct4(S229) at the onset of G2/M phase, inducing 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. Furthermore, Aurkb phosphormimetic and PP1 binding-deficient mutations in Oct4 disrupt the pluripotent cell cycle, lead to the loss of pluripotency in ESCs, and decrease the efficiency of somatic cell reprogramming. Based on our findings, we suggest that the cell cycle is directly linked to pluripotency programs in ESCs. [BMB Reports 2016; 49(10): 527-528].
在胚胎干细胞（ESC）中，细胞周期调控与多能性密切相关。特别是，维持多能性转录程序所必需的核心转录因子（CTF）在M/G1期转换过程中应被重置。然而，CTF在细胞周期进程中是如何被调控的仍不清楚。在此，我们描述了在细胞周期中极光激酶b（Aurkb）/蛋白磷酸酶1（PP1）轴对Oct4的调控对于将Oct4重置为多能性以及在确定ESC身份时与细胞周期相关的靶基因很重要。Aurkb在G2/M期开始时磷酸化Oct4（S229），诱导Oct4从染色质上解离，而PP1在M/G1期转换期间结合Oct4并使Oct4（S229）去磷酸化，这重置了Oct4驱动的多能性转录和细胞周期。此外，Oct4中的Aurkb磷酸模拟和PP1结合缺陷突变破坏了多能细胞周期，导致ESC多能性丧失，并降低了体细胞重编程的效率。基于我们的发现，我们认为细胞周期与ESC中的多能性程序直接相关。[《BMB报告》2016年；49(10):527 - 528]
