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Cell Rep. 2018 Mar 6;22(10):2615-2627. doi: 10.1016/j.celrep.2018.02.040.

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

Author information

1
Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
2
Nuclear Dynamics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
3
Bioinformatics Group, Babraham Institute, Cambridge CB22 3AT, UK.
4
Nuclear Dynamics Programme, Babraham Institute, Cambridge CB22 3AT, UK; Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
5
Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK; Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK. Electronic address: peter.rugg-gunn@babraham.ac.uk.

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.

KEYWORDS:

chromatin looping; differentiation; epigenetics; gene regulation; genome organization; pluripotency; promoter capture Hi-C

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