TY - JOUR
T1 - Transcription factor cooperativity in early adipogenic hotspots and super-enhancers
AU - Siersbæk, Rasmus
AU - Rabiee, Atefeh
AU - Nielsen, Ronni
AU - Sidoli, Simone
AU - Traynor, Sofie
AU - Loft, Anne
AU - Poulsen, Lars La Cour
AU - Rogowska-Wrzesinska, Adelina
AU - Jensen, Ole N.
AU - Mandrup, Susanne
N1 - Funding Information:
The authors are grateful to members of the Mandrup and Jensen groups for valuable discussions. In particular, the authors thank Mads M. Aagaard, Anders K. Haakonsson, Søren F. Schmidt, and Jesper G. Madsen for assistance with bioinformatics analyses. We also thank Dr. Huck-Hui Ng for the generous gift of the KLF5 antibody. This work was in part carried out at the Villum Center for Bioanalytical Sciences, Department of Biochemistry and Molecular Biology, SDU, supported by the Villum Foundation. Work in the Mandrup laboratory was supported by grants from the Danish Independent Research Council | Natural Sciences and the Novo Nordisk Foundation, and work in the Jensen laboratory was financed by the Danish National Research Foundation (grant DNRF82 to the Center for Epigenetics).
PY - 2014/6/12
Y1 - 2014/6/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2014.04.042
DO - 10.1016/j.celrep.2014.04.042
M3 - Article
AN - SCOPUS:84902302671
SN - 2211-1247
VL - 7
SP - 1443
EP - 1455
JO - Cell Reports
JF - Cell Reports
IS - 5
ER -