TRIM72 is known to be involved in the negative feedback regulation of myogenesis by targeting insulin receptor substrate-1. Here, we found that TRIM72 was more highly expressed in oxidative muscle with the higher activity of MEF2, compared to glycolytic muscle. Indeed, TRIM72 promoter contained an evolutionarily conserved MEF2 site juxtaposed to E-box. TRIM72 promoter activity was decreased by the site-directed mutagenesis of either E-boxes or a MEF2 site and synergistically enhanced by MyoD (or myogenin) and MEF2, which were associated with proximal E-box, and MEF2 site of the TRIM72 promoter, respectively. Taken together all these data, we concluded that the synergism of MyoD (or myogenin) and MEF2 is necessary for TRIM72 expression during C2C12 differentiation. (C) 2010 Elsevier Inc. All rights reserved.