Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program
Open accessAbstract
Skeletal muscle tissue shows an extraordinary cellular plasticity, but the underlying molecular mechanisms are still poorly understood. Here, we use a combination of experimental and computational approaches to unravel the complex transcriptional network of muscle cell plasticity centered on the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a regulatory nexus in endurance training adaptation. By integrating data on genome-wide binding of PGC-1α and gene expression upon PGC-1α overexpression with comprehensive computational prediction of transcription factor binding sites (TFBSs), we uncover a hitherto-underestimated number of transcription factor partners involved in mediating PGC-1α action. In particular, principal component analysis of TFBSs at PGC-1α binding regions predicts that, besides the well-known role of the estrogen-related receptor α (ERRα), the activator protein 1 complex (AP-1) plays a major role in regulating the PGC-1α-controlled gene program of the hypoxia response. Our findings thus reveal the complex transcriptional network of muscle cell plasticity controlled by PGC-1α.
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Elevated intracellular Ca2+ levels cause activation of AP-1 in hypoxia in a HIF-independent manner.
“Interestingly, elevated intracellular Ca2+ levels caused activation of AP-1 in hypoxia in a HIF-independent manner.”
From HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells (2021) · cites this paper as [212]
The section on functional interaction between PGC-1α and AP-1 reports that their joint targets are enriched for a response to hypoxia. It does not say that elevated intracellular Ca2+ activates AP-1. The Discussion describes HIF-1α-independent angiogenesis mediated by PGC-1α, but does not establish that AP-1 activation in hypoxia is HIF-independent. Page numbers were unavailable in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredAP-1 acts together with the Estrogen Related Receptor to activate transcription of PGC-1α.
“it was reported to act together with the Estrogen Related Receptor to activate transcription of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) [44].”
From 20-Hydroxyecdysone Boosts Energy Production and Biosynthetic Processes in Non-Transformed Mouse Cells (2024) · cites this paper as [44]
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HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells
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- Authors
- Baresic, M., Salatino, S., Kupr, B., van Nimwegen, E., & Handschin, C.
- Affiliations
- Focal Area Growth and Development, Biozentrum, University of Basel
- SIB Swiss Institute of Bioinformatics (CH)
- University of Basel (CH)
- Focal Area Computational and Systems Biology, Biozentrum, University of Basel
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2014-08-01
- Volume
- 34
- Issue
- 16
- Pages
- 2996-3012
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC4135604
- OpenAlex
- W2104219345
- Cited by
- 40
- References
- 49
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 1 · 2022: 1 · 2021: 4 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 9 · 2015: 3
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- edoc (University of Basel)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (135397)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- PGC-1α, AP-1, transcriptional regulatory networks, skeletal muscle plasticity, endurance training adaptation, hypoxia response, transcription factor binding sites, estrogen-related receptor alpha, transcriptional coactivator, gene expression regulation
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, ERRalpha Estrogen-Related Receptor, Animals, Binding Sites, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Receptors, Estrogen, Transcription Factors, Cell Hypoxia, Muscle Fibers, Skeletal, Transcription Factor AP-1, Principal Component Analysis, RNA Interference, PPAR gamma, Mice, Gene Regulatory Networks
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