Long-Range Enhancer Interactions Are Prevalent in Mouse Embryonic Stem Cells and Are Reorganized upon Pluripotent State Transition.
Wingett, Steven W
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Novo, C., Javierre, B., Cairns, J., Segonds-Pichon, A., Wingett, S. W., Freire-Pritchett, P., Furlan-Magaril, M., et al. (2018). Long-Range Enhancer Interactions Are Prevalent in Mouse Embryonic Stem Cells and Are Reorganized upon Pluripotent State Transition.. Cell Rep, 22 (10), 2615-2627. https://doi.org/10.1016/j.celrep.2018.02.040
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.
Pluripotent Stem Cells, Germ Layers, Animals, Mice, Cell Differentiation, Protein Binding, Gene Regulatory Networks, Enhancer Elements, Genetic, Promoter Regions, Genetic, Mouse Embryonic Stem Cells, Nanog Homeobox Protein
P.J.R.-G. is supported by the Wellcome Trust (WT093736), Biotechnology and Biological Sciences Research Council (BB/M022285/1 and BB/P013406/1), and the European Commission Network of Excellence EpiGeneSys (HEALTH-F4-2010-257082). This work was also supported by the following grants to P.F.: Medical Research Council (MR/L007150/1, MC_UP_1302/1, MC_UP_1302/3, MC_UP_1302/5), and Biotechnology and Biological Sciences Research Council (BB/J004480/1).
Medical Research Council (MC_PC_12009)
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External DOI: https://doi.org/10.1016/j.celrep.2018.02.040
This record's URL: https://www.repository.cam.ac.uk/handle/1810/275704
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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