Rasmus Siersbæk1,‡, Jesper G. S. Madsen1,‡, Biola M. Javierre2,‡, Ronni Nielsen1,‡, Emilie K. Bagge1, Jonathan Cairns2, Steven W. Wingett2,3, Sofie Traynor1, Mikhail Spivakov2, Peter Fraser2§, Susanne Mandrup1§
1 University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
2 Nuclear Dynamics Programme, Babraham Institute, Cambridge, CB22 3AT, UK.
3 Bioinformatics Group, Babraham Institute, Cambridge, CB22 3AT, UK.
‡ Co-first author
§ Co-corresponding authors: s.mandrup@bmb.sdu.dk, peter.fraser@babraham.ac.uk
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 4h after induction of 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.
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