Reorganization of Enhancer Patterns in Transition from Naive to Primed Pluripotency
Buecker, Christa1; Srinivasan, Rajini1; Wu, Zhixiang2; Calo, Eliezer1; Acampora, Dario3,4; Faial, Tiago1; Simeone, Antonio3,4; Tan, Minjia2; Swigut, Tomasz1; Wysocka, Joanna1,5
刊名CELL STEM CELL
2014-06-05
卷号14期号:6页码:838-853
ISSN号1934-5909
DOI10.1016/j.stem.2014.04.003
文献子类Article
英文摘要Naive and primed pluripotency is characterized by distinct signaling requirements, transcriptomes, and developmental properties, but both cellular states share key transcriptional regulators: Oct4, Sox2, and Nanog. Here, we demonstrate that transition between these two pluripotent states is associated with widespread Oct4 relocalization, mirrored by global rearrangement of enhancer chromatin landscapes. Our genomic and biochemical analyses identified candidate mediators of primed state-specific Oct4 binding, including Otx2 and Zic2/3. Even when differentiation cues are blocked, premature Otx2 overexpression is sufficient to exit the naive state, induce transcription of a substantial subset of primed pluripotency-associated genes, and redirect Oct4 to previously inaccessible enhancer sites. However, the ability of Otx2 to engage new enhancer regions is determined by its levels, cis-encoded properties of the sites, and the signaling environment. Our results illuminate regulatory mechanisms underlying pluripotency and suggest that the capacity of transcription factors such as Otx2 and Oct4 to pioneer new enhancer sites is highly context dependent.
资助项目NIH[P01 GM099130] ; California Institute for Regenerative Medicine (CIRM)[RB3-05100] ; Stanford Genome Training Program[5 T32 HG 44-17] ; Italian Association for Cancer Research (AIRC)[IG2013 N. 14152] ; CNR-MIUR Epigenetics Flagship[00000000]
WOS关键词EMBRYONIC STEM-CELLS ; MASTER TRANSCRIPTION FACTORS ; COLLABORATIVE COMPETITION ; INTERACTION NETWORK ; STATE ; CHROMATIN ; EPIBLAST ; BINDING ; OCT4 ; PATHWAYS
WOS研究方向Cell Biology
语种英语
出版者CELL PRESS
WOS记录号WOS:000341248500019
内容类型期刊论文
源URL[http://119.78.100.183/handle/2S10ELR8/277030]  
专题化学蛋白质组学研究中心
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Swigut, Tomasz
作者单位1.Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA;
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
3.CNR, Inst Genet & Biophys Adriano Buzzati Traverso, I-80131 Naples, Italy;
4.IRCCS Neuromed, I-86077 Pozzilli, IS, Italy;
5.Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA
推荐引用方式
GB/T 7714
Buecker, Christa,Srinivasan, Rajini,Wu, Zhixiang,et al. Reorganization of Enhancer Patterns in Transition from Naive to Primed Pluripotency[J]. CELL STEM CELL,2014,14(6):838-853.
APA Buecker, Christa.,Srinivasan, Rajini.,Wu, Zhixiang.,Calo, Eliezer.,Acampora, Dario.,...&Wysocka, Joanna.(2014).Reorganization of Enhancer Patterns in Transition from Naive to Primed Pluripotency.CELL STEM CELL,14(6),838-853.
MLA Buecker, Christa,et al."Reorganization of Enhancer Patterns in Transition from Naive to Primed Pluripotency".CELL STEM CELL 14.6(2014):838-853.
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