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Mol Cell. 2017 May 4;66(3):420-435.e5. doi: 10.1016/j.molcel.2017.04.010.

Dynamic Rewiring of Promoter-Anchored Chromatin Loops during Adipocyte Differentiation.

Author information

1
University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
2
Nuclear Dynamics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
3
Nuclear Dynamics Programme, Babraham Institute, Cambridge CB22 3AT, UK; Bioinformatics Group, Babraham Institute, Cambridge CB22 3AT, UK.
4
Nuclear Dynamics Programme, Babraham Institute, Cambridge CB22 3AT, UK; Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA. Electronic address: peter.fraser@babraham.ac.uk.
5
University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark. Electronic address: s.mandrup@bmb.sdu.dk.

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.

KEYWORDS:

ChIP-seq; adipocyte differentiation; chromatin looping; corepressors; poised enhancers; promoter capture Hi-C; single nucleotide variance; super-enhancers; topologically associating domains; transcriptional regulation

PMID:
28475875
DOI:
10.1016/j.molcel.2017.04.010
[Indexed for MEDLINE]
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