1. Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program.
- Author
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Baresic M, Salatino S, Kupr B, van Nimwegen E, and Handschin C
- Subjects
- Animals, Binding Sites genetics, Cell Hypoxia genetics, Cell Line, DNA-Binding Proteins genetics, Gene Expression Regulation, Mice, PPAR gamma genetics, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Principal Component Analysis, RNA Interference, Receptors, Estrogen metabolism, Transcription Factor AP-1 genetics, ERRalpha Estrogen-Related Receptor, Gene Regulatory Networks, Muscle Fibers, Skeletal metabolism, Transcription Factor AP-1 metabolism, Transcription Factors genetics, Transcription Factors metabolism
- Abstract
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., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Published
- 2014
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