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 four hours after induction of differentiation of 3T3-L1 preadipocytes. This reorganization is tightly coupled to dynamic changes in target gene expression. The formation of promoter-enhancer loops is tightly linked to the 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. 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. Overall design: We performed Hi-C and promoter capture Hi-C (PCHi-C) to investigate the dynamics of the 3D chromatin structure during adipocyte differentiation. We used mRNA-seq to identify changes in gene expression and ChIP-seq to map the chromatin binding of transcriptional regulators and epigenomic marks.