Cited by 272Peroxisome Proliferator-Activated ReceptorsAdipose Tissue and MetabolismGenomics and Chromatin Dynamics

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Peroxisome Proliferator-Activated Receptor γ and C/EBPα Synergistically Activate Key Metabolic Adipocyte Genes by Assisted Loading

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Madsen, Maria Stahl, Siersbæk, Rasmus, Boergesen, Michael, Nielsen, Ronni, Mandrup, Susanne·2014·Molecular and Cellular Biology

DOI 10.1128/mcb.01344-13PMC PMC3958030

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Abstract

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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Authors: Madsen, M. S., Siersbæk, R., Boergesen, M., Nielsen, R., & Mandrup, S.
Affiliations: University of Southern Denmark (DK)
ORCID: Madsen, Maria Stahl
Siersbæk, Rasmus
Nielsen, Ronni
Mandrup, Susanne
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
DOI: 10.1128/mcb.01344-13
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
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
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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Peroxisome Proliferator-Activated Receptor γ and C/EBPα Synergistically Activate Key Metabolic Adipocyte Genes by Assisted Loading

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