Functional interaction between peroxisome proliferator-activated receptors-a and Mef-2C on human carnitine palmitoyltransferase 1b (CPT1b) gene activation

Muscle-type carnitine palmitoyltransferase 1 (CPT1b) is considered to be the gene that controls fatty acid mitochondrial b-oxidation. A functional peroxisome proliferator-activated receptor (PPAR) responsive element (PPRE) and a myocite-specific (MEF2) site that binds MEF2A and MEF2C in the promoter of this gene had been previously identified. We investigated the roles of the PPRE and the MEF2 binding sites and the potential interaction between PPARa and MEF2C regulating the CPT1b gene promoter. Mutation analysis indicated that the MEF2 site contributed to the activation of the CPT1b promoter by PPAR in C2C12 cells. The reporter construct containing the PPRE and the MEF2C site was synergistically activated by co-expression of PPAR, retinoid X receptor (RXR) and MEF2C in non-muscle cells. Moreover, protein-binding assays demonstrated that MEF2C and PPAR specifically bound to one another in vitro. Also for the synergistic activation of the CPT1b gene promoter by MEF2C and PPARaRXRa, a precise arrangement of its binding sites was essential.