Long-Range Enhancer Interactions Are Prevalent in Mouse Embryonic Stem Cells and Are Reorganized upon Pluripotent State Transition.
Long-Range Enhancer Interactions Are Prevalent in Mouse Embryonic Stem Cells and Are Reorganized upon Pluripotent State Transition.
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DOI：
10.1016/j.celrep.2018.02.040
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发表时间：
2018-03-06
期刊：
影响因子：
8.8
通讯作者：
Rugg-Gunn PJ
中科院分区：
文献类型：
--
作者：
Novo CL;Javierre BM;Cairns J;Segonds-Pichon A;Wingett SW;Freire-Pritchett P;Furlan-Magaril M;Schoenfelder S;Fraser P;Rugg-Gunn PJ
转录增强子，包括超级增强子（SE），与启动子形成物理相互作用以调节细胞类型特异性基因表达。SE的特征在于高转录因子占有率和大的活性染色质结构域，并且它们通常使用计算预测分配给靶启动子。启动子-SE相互作用如何在细胞状态转换时改变，以及转录因子是否维持SE相互作用，尚未报道。在这里，我们使用启动子捕获Hi-C来识别与小鼠胚胎干细胞（ESC）中的SE相互作用的启动子。我们发现SE形成复杂的空间网络，其中单个SE接触多个启动子，并且多能状态之间发生启动子-SE相互作用的重新布线。我们还表明，远程启动子-SE相互作用在ESC中比在上胚层干细胞（EpiSC）或Nanog缺陷型ESC中更普遍。我们的结论是，SE形成细胞类型特异性的相互作用网络，部分依赖于核心转录因子，从而为多能细胞的基因调控组织提供了见解。启动子捕获Hi-C鉴定小鼠多能细胞中的3D相互作用超级增强子（SE）形成接触多个启动子的复杂空间网络ESC和EpiSC多能状态之间启动子-SE相互作用的重新布线长程SE相互作用是小鼠ESC的标志Novo et al.使用启动子捕获Hi-C定位小鼠多能细胞中超级增强子（SE）的靶启动子。SE形成复杂的网络，并且启动子-SE相互作用的子集在ESC和EpiSC之间重新连接。在ESC中，许多SE形成在EpiSC或Nanog缺陷型ESC中未检测到的长程接触。
Transcriptional enhancers, including super-enhancers (SEs), form physical interactions with promoters to regulate cell-type-specific gene expression. SEs are characterized by high transcription factor occupancy and large domains of active chromatin, and they are commonly assigned to target promoters using computational predictions. How promoter-SE interactions change upon cell state transitions, and whether transcription factors maintain SE interactions, have not been reported. Here, we used promoter-capture Hi-C to identify promoters that interact with SEs in mouse embryonic stem cells (ESCs). We found that SEs form complex, spatial networks in which individual SEs contact multiple promoters, and a rewiring of promoter-SE interactions occurs between pluripotent states. We also show that long-range promoter-SE interactions are more prevalent in ESCs than in epiblast stem cells (EpiSCs) or Nanog-deficient ESCs. We conclude that SEs form cell-type-specific interaction networks that are partly dependent on core transcription factors, thereby providing insights into the gene regulatory organization of pluripotent cells. Promoter-capture Hi-C identifies 3D interactions in mouse pluripotent cells Super-enhancers (SEs) form complex spatial networks contacting multiple promoters Rewiring of promoter-SE interactions between ESC and EpiSC pluripotent states Long-range SE interactions are a hallmark of mouse ESCs Novo et al. use promoter-capture Hi-C to map the target promoters of super-enhancers (SEs) in mouse pluripotent cells. SEs form complex networks, and a subset of promoter-SE interactions was rewired between ESCs and EpiSCs. In ESCs, many SEs form long-range contacts that are not detected in EpiSC or Nanog-deficient ESCs.
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影响因子：
7.7
作者：
Freire-Pritchett P;Schoenfelder S;Várnai C;Wingett SW;Cairns J;Collier AJ;García-Vílchez R;Furlan-Magaril M;Osborne CS;Fraser P;Rugg-Gunn PJ;Spivakov M
通讯作者：
Spivakov M
DOI：
10.1038/nrm3949
发表时间：
2015-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
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通讯作者：
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影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
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影响因子：
64.8
作者：
Brons, I. Gabrielle M.;Smithers, Lucy E.;Vallier, Ludovic
通讯作者：
Vallier, Ludovic
影响因子：
4.6
作者：
Guo, Ge;Yang, Jian;Smith, Austin
通讯作者：
Smith, Austin