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Novo, Clara Lopes; Javierre, Biola-Maria; Cairns, Jonathan; Segonds-Pichon, Anne; Wingett, Steven W; Freire-Pritchett, Paula; Furlan-Magaril, Mayra; Schoenfelder, Stefan; Fraser, Peter; Rugg-Gunn, Peter J (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
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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.