Dynamic rewiring of promoter-anchored chromatin loops during adipocyte differentiation

Rasmus Siersbæk^1,‡, Jesper G. S. Madsen^1,‡, Biola M. Javierre^2,‡, Ronni Nielsen^1,‡, Emilie K. Bagge¹, Jonathan Cairns², Steven W. Wingett^2,3, Sofie Traynor¹, Mikhail Spivakov², Peter Fraser^2§, Susanne Mandrup^1§

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

Abstract

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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Links to relavant sites

Full-length manuscript
NCBI GEO
Mandrup group website