Transcription factor cooperativity in early adipogenic hotspots and super-enhancers

Rasmus Siersbæk, Atefeh Rabiee, Ronni Nielsen, Simone Sidoli, Sofie Traynor, Anne Loft, Lars La Cour Poulsen, Adelina Rogowska-Wrzesinska, Ole N. Jensen, Susanne Mandrup

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

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 (~400bp) 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-enhancersconstitute important regulatory hubs that serve to integrate external stimuli on chromatin.

Original languageEnglish (US)
Pages (from-to)1443-1455
Number of pages13
JournalCell Reports
Volume7
Issue number5
DOIs
StatePublished - Jun 12 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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