Cited by 234Genomics and Chromatin DynamicsChromatin Remodeling and CancerEpigenetics and DNA Methylation

Transcription Factor Cooperativity in Early Adipogenic Hotspots and Super-Enhancers

Open access
Siersbæk, Rasmus, Rabiee, Atefeh, Nielsen, Ronni, Sidoli, Simone, Traynor, Sofie, Loft, Anne, Poulsen, Lars La Cour, Rogowska-Wrzesinska, Adelina +2 more·2014·Cell Reports

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.

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Crossref · 10.1016/j.celrep.2014.04.042

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  • Transcription factor hotspots, such as R1 and R2, create a permissive chromatin environment for the emergence of new transcription factor binding regions.

    “Indeed, it has been proposed that transcription factor hotspots, such as R1 and R2, create a permissive chromatin environment for the emergence of new transcription factor binding regions6.”

    From Genetic dissection of the α-globin super-enhancer in vivo (2016) · cites this paper as [6]

    The Discussion (page unavailable) says transcription factors at hotspots cooperate in chromatin remodeling and establish an active epigenomic signature, supporting the idea of a permissive chromatin environment. Our copy does not identify hotspots R1 and R2 or say that hotspots enable new transcription factor binding regions to emerge. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Authors
Siersbæk, R., Rabiee, A., Nielsen, R., Sidoli, S., Traynor, S., Loft, A., Poulsen, L. L. C., Rogowska-Wrzesinska, A., Jensen, O. N., & Mandrup, S.
Affiliations
University of Southern Denmark (DK)
Corresponding author
Mandrup, Susanne
Venue
Cell Reports
Publisher
Elsevier BV
Published
2014-06
Volume
7
Issue
5
Pages
1443-1455
ISSN
2211-1247 (ISSN-L)
OpenAlex
W1981491540
Cited by
234
References
57
Citations by year
2026: 7 · 2025: 9 · 2024: 11 · 2023: 21 · 2022: 16 · 2021: 23 · 2020: 18 · 2019: 16 · 2018: 24 · 2017: 21 · 2016: 29 · 2015: 30 · 2014: 9
FWCI
12.17
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Scholarly Commons (University of the Pacific) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
Funders
  • Novo Nordisk Fonden
  • Danmarks Grundforskningsfond (DNRF82)
  • Shanxi Datong University
  • Villum Fonden
  • Danmarks Frie Forskningsfond
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
transcription factor cooperativity, super-enhancers, adipogenesis, enhancer activity, transcriptional reprogramming, chromatin regulation
MeSH terms
Animals, Enhancer Elements, Genetic, Protein Binding, Transcription Factors, Transcriptional Activation, 3T3 Cells, Genome, Gene Expression Regulation, Developmental, Adipogenesis, Mice

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