Functional relationship between MyoD and peroxisome proliferator-activated receptor-dependent regulatory pathways in the control of the human uncoupling protein-3 gene transcription

Uncoupling protein-3 (UCP3) gene is a member of the mitochondrial carrier superfamily preferentially expressed in skeletal muscle and up-regulated by fatty acids. Peroxisome proliferator-activated re-ceptor (PPAR) and PPAR (also known as PPAR) mediate human UCP3 gene regulation by fatty ac-ids through a direct-repeat (DR-1) element in the promoter. DR-1 mutation renders UCP3 promoter unresponsive to PPAR ligand in vitro and consis-tently blocks gene induction by fatty acids in vivo. Although they act through separate sites in the promoter, MyoD and PPAR-dependent regulatory pathways are functionally connected: only in the presence of MyoD, does UCP3 become sensitive to PPAR ligand-dependent regulation. MyoD control