Journal
CELL REPORTS
Volume 22, Issue 10, Pages 2615-2627Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.02.040
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Funding
- Wellcome Trust [WT093736]
- Biotechnology and Biological Sciences Research Council [BB/M022285/1, BB/P013406/1, BB/J004480/1]
- European Commission Network of Excellence EpiGeneSys [HEALTH-F4-2010-257082]
- Medical Research Council [MR/L007150/1, MC_UP_1302/1, MC_UP_1302/3, MC_UP_1302/5]
- Biotechnology and Biological Sciences Research Council [BBS/E/B/000C0421, BBS/E/B/000C0422, BB/M022285/1] Funding Source: researchfish
- Medical Research Council [MC_UP_1302/1, MC_PC_12009] Funding Source: researchfish
- BBSRC [BB/M022285/1, BBS/E/B/000C0421, BBS/E/B/000C0422] Funding Source: UKRI
- MRC [MR/L007150/1, MC_UP_1302/3, MC_EX_MR/S300002/1] Funding Source: UKRI
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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.
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