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Cell Rep. 2014 Jun 12;7(5):1443-1455. doi: 10.1016/j.celrep.2014.04.042. Epub 2014 May 22.

Transcription factor cooperativity in early adipogenic hotspots and super-enhancers.

Author information

1
Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
2
Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark. Electronic address: s.mandrup@bmb.sdu.dk.

Abstract

It is becoming increasingly clear that transcription factors operate in complex networks through thousands of genomic binding sites, many of which bind several transcription factors. However, the extent and mechanisms of crosstalk between transcription factors at these hotspots remain unclear. Using a combination of advanced proteomics and genomics approaches, we identify ∼12,000 transcription factor hotspots (∼400 bp) in the early phase of adipogenesis, and we find evidence of both simultaneous and sequential binding of transcription factors at these regions. We demonstrate that hotspots are highly enriched in large super-enhancer regions (several kilobases), which drive the early adipogenic reprogramming of gene expression. Our results indicate that cooperativity between transcription factors at the level of hotspots as well as super-enhancers is very important for enhancer activity and transcriptional reprogramming. Thus, hotspots and super-enhancers constitute important regulatory hubs that serve to integrate external stimuli on chromatin.

PMID:
24857652
DOI:
10.1016/j.celrep.2014.04.042
[Indexed for MEDLINE]
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