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

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 ? coactivator 1? (PGC-1?), a regulatory nexus in endurance training adaptation. By integrating data on genome-wide binding of PGC-1? and gene expression upon PGC-1? 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-1? action. In particular, principal component analysis of TFBSs at PGC-1? binding regions predicts that, besides the well-known role of the estrogen-related receptor ? (ERR?), the activator protein 1 complex (AP-1) plays a major role in regulating the PGC-1?-controlled gene program of the hypoxia response. Our findings thus reveal the complex transcriptional network of muscle cell plasticity controlled by PGC-1?.

SUBMITTER: Baresic M 

PROVIDER: S-EPMC4135604 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature