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Publication : Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program.

First Author  Baresic M Year  2014
Journal  Mol Cell Biol Volume  34
Issue  16 Pages  2996-3012
PubMed ID  24912679 Mgi Jnum  J:224275
Mgi Id  MGI:5661805 Doi  10.1128/MCB.01710-13
Citation  Baresic M, et al. (2014) Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1alpha in the regulation of the hypoxic gene program. Mol Cell Biol 34(16):2996-3012
abstractText  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 gamma coactivator 1alpha (PGC-1alpha), a regulatory nexus in endurance training adaptation. By integrating data on genome-wide binding of PGC-1alpha and gene expression upon PGC-1alpha 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-1alpha action. In particular, principal component analysis of TFBSs at PGC-1alpha binding regions predicts that, besides the well-known role of the estrogen-related receptor alpha (ERRalpha), the activator protein 1 complex (AP-1) plays a major role in regulating the PGC-1alpha-controlled gene program of the hypoxia response. Our findings thus reveal the complex transcriptional network of muscle cell plasticity controlled by PGC-1alpha.
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