SRA

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 1a (PGC-1a), a regulatory nexus in endurance training adaptation. By integrating data on genome-wide binding of PGC-1a and gene expression upon PGC-1a over-expression with comprehensive computational prediction of transcription factor binding sites (TFBSs), we uncover a hitherto underestimated number of transcription factor partners involved in mediating PGC-1a action. In particular, principal component analysis of TFBSs at PGC-1a binding regions predicts that, besides the well-known role of the estrogen-related receptor a (ERRa), the activator protein-1 complex (AP-1) plays a major role in regulating the PGC-1a-controlled gene program of hypoxia response. Our findings thus reveal the complex transcriptional network of muscle cell plasticity controlled by PGC-1a. Overall design: We performed ChIP-Seq experiments to identify all DNA recruitment sites for PGC-1alpha in C2C12 cells on genome-wide scale. The experiment was performed in duplicate and the Whole Cell Extract (WCE; =input DNA) was used as background condition.