Activation of nuclear receptor coactivator PGC-1α by arginine methylation

Peroxisome proliferator-activated receptor gamma coactivator la (PGC-1 alpha.), a tissue-specific and inducible transcriptional coactivator for several nuclear receptors, plays a key role in energy metabolism. We report here that PGC-1 alpha coactivator activity is potentiated by arginine methylation by protein arginine methyltransferase 1 (PRMT1), another nuclear receptor coactivator. Mutation of three substrate arginines in the C-terminal region of PGC-1 alpha abolished the cooperative coactivator function of PGC-1 alpha and PRMT1, and compromised the ability of PGC-1 alpha to induce endogenous target genes. Finally, endogenous PRMT1 contributes to PGC-1 alpha coactivator activity, and to the induction of genes important for mitochondrial biogenesis.