Document Type

Article

Publication Title

Cell Reports

ISSN

2211-1247

Volume

7

Issue

5

DOI

10.1016/j.celrep.2014.04.042

First Page

1443

Last Page

1455

Publication Date

6-12-2014

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. © 2014 The Authors.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Share

COinS