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Long-Range Enhancer Interactions Are Prevalent in Mouse Embryonic Stem Cells and Are Reorganized upon Pluripotent State Transition.

Published version
Peer-reviewed

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Authors

Novo, Clara Lopes 
Javierre, Biola-Maria 
Cairns, Jonathan 
Segonds-Pichon, Anne 
Wingett, Steven W 

Abstract

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.

Description

Keywords

chromatin looping, differentiation, epigenetics, gene regulation, genome organization, pluripotency, promoter capture Hi-C, Animals, Cell Differentiation, Enhancer Elements, Genetic, Gene Regulatory Networks, Germ Layers, Mice, Mouse Embryonic Stem Cells, Nanog Homeobox Protein, Pluripotent Stem Cells, Promoter Regions, Genetic, Protein Binding

Journal Title

Cell Rep

Conference Name

Journal ISSN

2211-1247
2211-1247

Volume Title

22

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MC_PC_12009)
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).