Transcription factor cooperativity in early adipogenic hotspots and super-enhancers

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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.

OriginalsprogEngelsk
TidsskriftCell Reports
Vol/bind7
Udgave nummer5
Sider (fra-til)1443–1455
Antal sider13
DOI
StatusUdgivet - 12. jun. 2014

Fingeraftryk

Dyk ned i forskningsemnerne om 'Transcription factor cooperativity in early adipogenic hotspots and super-enhancers'. Sammen danner de et unikt fingeraftryk.

Citationsformater