Otx2 and Oct4 drive early enhancer activation during embryonic stem cell transition from naive pluripotency.
Otx2 and Oct4 drive early enhancer activation during embryonic stem cell transition from naive pluripotency.
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DOI：
10.1016/j.celrep.2014.05.037
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发表时间：
2014-06-26
期刊：
影响因子：
8.8
通讯作者：
Sharrocks AD
中科院分区：
文献类型：
--
作者：
Yang SH;Kalkan T;Morissroe C;Marks H;Stunnenberg H;Smith A;Sharrocks AD
胚胎干细胞（ESCs）的独特之处在于它们具有分化成体内所有细胞类型的能力。我们对在自我更新条件下维持幼稚多能状态的复杂转录控制回路了解很多，但对细胞如何响应分化刺激而退出这种状态的了解相对较少。在这里，我们研究了Otx 2在小鼠胚胎干细胞中的作用，并证明它在重塑基因调控网络中起着主导作用，因为细胞退出基态多能性。otx 2通过影响染色质标记和相关基因的活性来驱动增强子激活。从机制上讲，Oct 4是Otx 2表达所必需的，而Otx 2是Oct 4有效募集到许多增强子区域所必需的。因此，Oct 4-Otx 2调节轴在伴随从基态多能性退出的早期事件期间积极地建立新的调节染色质景观。转录因子Otx 2在分化小鼠ESC中驱动增强子激活Oct 4控制Otx 2表达水平Otx 2与Oct 4在增强子激活中协作Otx 2有助于增强子维持和从头激活转录因子Otx 2在神经发育和胚胎干细胞从多能基态退出中起重要作用。在这项研究中，杨等。证明Otx 2驱动增强子激活和维持在早期细胞命运转变远离基态多能性。Otx 2参与与Oct 4的调节伙伴关系，其中Oct 4最初促进Otx 2表达。Otx 2随后将Oct 4招募到增强子的一个子集，并建立了一个调节染色质景观。
Embryonic stem cells (ESCs) are unique in that they have the capacity to differentiate into all of the cell types in the body. We know a lot about the complex transcriptional control circuits that maintain the naive pluripotent state under self-renewing conditions but comparatively less about how cells exit from this state in response to differentiation stimuli. Here, we examined the role of Otx2 in this process in mouse ESCs and demonstrate that it plays a leading role in remodeling the gene regulatory networks as cells exit from ground state pluripotency. Otx2 drives enhancer activation through affecting chromatin marks and the activity of associated genes. Mechanistically, Oct4 is required for Otx2 expression, and reciprocally, Otx2 is required for efficient Oct4 recruitment to many enhancer regions. Therefore, the Oct4-Otx2 regulatory axis actively establishes a new regulatory chromatin landscape during the early events that accompany exit from ground state pluripotency. Transcription factor Otx2 drives enhancer activation in differentiating mouse ESCs Oct4 controls Otx2 expression levels Otx2 collaborates with Oct4 in enhancer activation Otx2 contributes to enhancer maintenance and de novo activation The transcription factor Otx2 plays an important role in neural development and in the exit of embryonic stem cells from the pluripotent ground state. In this study, Yang et al. demonstrate that Otx2 drives enhancer activation and maintenance during the early cell-fate transition away from ground state pluripotency. Otx2 is involved in a regulatory partnership with Oct4 wherein Oct4 initially promotes Otx2 expression. Otx2 subsequently recruits Oct4 to a subset of enhancers and establishes a regulatory chromatin landscape.
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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
影响因子：
4.8
作者：
Armstrong, Lyle
通讯作者：
Armstrong, Lyle
影响因子：
21.3
作者：
Boroviak T;Loos R;Bertone P;Smith A;Nichols J
通讯作者：
Nichols J
影响因子：
64.5
作者：
Gifford CA;Ziller MJ;Gu H;Trapnell C;Donaghey J;Tsankov A;Shalek AK;Kelley DR;Shishkin AA;Issner R;Zhang X;Coyne M;Fostel JL;Holmes L;Meldrim J;Guttman M;Epstein C;Park H;Kohlbacher O;Rinn J;Gnirke A;Lander ES;Bernstein BE;Meissner A
通讯作者：
Meissner A
影响因子：
64.8
作者：
Pasini, Diego;Cloos, Paul A. C.;Helin, Kristian
通讯作者：
Helin, Kristian