Dynamic Rewiring of Promoter-Anchored Chromatin Loops during Adipocyte Differentiation

Interactions between transcriptional promoters and their distal regulatory elements play an important role in transcriptional regulation; however, the extent to which these interactions are subject to rapid modulations in response to signals is unknown. Here, we use promoter capture Hi-C to demonstrate a rapid reorganization of promoter-anchored chromatin loops within 4 hr after inducing differentiation of 3T3-L1 preadipocytes. The establishment of new promoter-enhancer loops is tightly coupled to activation of poised (histone H3 lysine 4 mono- and dimethylated) enhancers, as evidenced by the acquisition of histone H3 lysine 27 acetylation and the binding of MED1, SMC1, and P300 proteins to these regions, as well as to activation of target genes. Intriguingly, formation of loops connecting activated enhancers and promoters is also associated with extensive recruitment of corepressors such as NCoR and HDACs, indicating that this class of coregulators may play a previously unrecognized role during enhancer activation. [Display omitted] •Dynamic promoters and enhancers are connected through dynamic chromatin loops•Chromatin loop formation is coupled to activation of poised enhancers•Enhancer activation is associated with corepressor recruitment Siersbæk et al. demonstrate a rapid and dynamic rewiring of promoter-anchored chromatin loops during adipocyte differentiation, which is linked to changes in the activity of promoters and enhancers. Loop formation involves activation of poised enhancers and is associated with extensive recruitment of both coactivators and corepressors.