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 |
DOI | 10.1016/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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