Dynamic Rewiring of Promoter-Anchored Chromatin Loops during Adipocyte Differentiation

Rasmus Siersbæk, Jesper Grud Skat Madsen, Biola Maria Javierre, Ronni Nielsen, Emilie Kristine Bagge, Jonathan Cairns, Steven William Wingett, Sofie Traynor, Mikhail Spivakov, Peter Fraser, Susanne Mandrup

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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 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.

OriginalsprogEngelsk
TidsskriftMolecular Cell
Vol/bind66
Udgave nummer3
Sider (fra-til)420-435.e5
ISSN1097-2765
DOI
StatusUdgivet - 2017

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