Transcription Factor Cooperativity in Early Adipogenic Hotspots and Super-Enhancers
Open accessAbstract
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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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)
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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
- ORCID
- 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
- gold
- doi.org
- Licence
- 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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