The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
Peroxisome Proliferator-Activated Receptor γ and C/EBPα Synergistically Activate Key Metabolic Adipocyte Genes by Assisted Loading
Open accessAbstract
Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) are key activators of adipogenesis. They mutually induce the expression of each other and have been reported to cooperate in activation of a few adipocyte genes. Recently, genome-wide profiling revealed a high degree of overlap between PPARγ and C/EBPα binding in adipocytes, suggesting that cooperativeness could be mediated through common binding sites. To directly investigate the interplay between PPARγ and C/EBPα at shared binding sites, we established a fibroblastic model system in which PPARγ and C/EBPα can be independently expressed. Using RNA sequencing, we demonstrate that coexpression of PPARγ and C/EBPα leads to synergistic activation of many key metabolic adipocyte genes. This is associated with extensive C/EBPα-mediated reprogramming of PPARγ binding and vice versa in the vicinity of these genes, as determined by chromatin immunoprecipitation combined with deep sequencing. Our results indicate that this is at least partly mediated by assisted loading involving chromatin remodeling directed by the leading factor. In conclusion, we report a novel mechanism by which the key adipogenic transcription factors, PPARγ and C/EBPα, cooperate in activation of the adipocyte gene program.
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“Assisted loading has been described in various systems30–37.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [33]
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PPARγ and the global map of adipogenesis and beyond
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Metadata
- Authors
- Madsen, M. S., Siersbæk, R., Boergesen, M., Nielsen, R., & Mandrup, S.
- Affiliations
- University of Southern Denmark (DK)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2014-03-01
- Volume
- 34
- Issue
- 6
- Pages
- 939-954
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC3958030
- OpenAlex
- W2170714239
- Cited by
- 272
- References
- 69
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 38 · 2023: 39 · 2022: 34 · 2021: 28 · 2020: 19 · 2019: 15 · 2018: 14 · 2017: 15 · 2016: 9 · 2015: 14 · 2014: 7
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Funders
- Lundbeckfonden (R118-2012-11639)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- PPARγ, C/EBPα, transcriptional cooperativity, chromatin remodeling, adipocyte gene expression, adipogenesis, transcription factor binding sites, fibroblasts, metabolic genes, transcriptional regulation
- MeSH terms
- Animals, Binding Sites, Cell Line, Chromatin, Fibroblasts, Protein Binding, 3T3 Cells, Adipocytes, CCAAT-Enhancer-Binding Proteins, PPAR gamma, Mice
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