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

Transcriptional enhancers, including super-enhancers (SE), form physical interactions with promoters to regulate cell type-specific gene expression. SE are characterised by high transcription factor occupancy and large domains of active chromatin, and are currently assigned to target promoters using computational predictions. How promoter–SE interactions change upon cell state transitions, and whether transcription factors maintain SE interactions, has not been reported. Here, we used promoter-capture Hi-C to identify promoters in close physical proximity to SE in mouse embryonic stem cells (ESCs). SE form complex, spatial networks in which individual SE contact multiple promoters, and a rewiring of promoter–SE interactions occurs between ESC and EpiSC pluripotent states. Long-range promoter–SE interactions are a hallmark of ESCs and are dependent on the transcription factor NANOG. These results provide new insights into the gene regulatory organization of pluripotent cells and demonstrate the requirement for transcription factors in maintaining a subset of SE interactions. Overall design: Promoter capture Hi-C of mouse ESCs, EpiSCs and Nanog-/- ESCs. CHiP-Seq in mouse EpiSCs against Nanog, Oct4 and Sox2. RNA-seq of EpiSCvsESC / ESCvsBT12