Role of a SET/Smad7 Interaction in Skeletal Myogenesis

A look at the interaction between the histone chaperone SET/TAF-I and the TGF signalling inhibitor Smad7 in the context of skeletal muscle differentiation. Here we report that SET can function as an inhibitor of transcription for myogenic related genes, while the interaction with Smad7 relieves, and enhances transcription of those myogenic genes. In contrast to the myogenic genes, exogenous Smad7 had no effect on SETs capability to repress the cyclin D1 promoter. This may explain the enhancement of myogenesis with SET and Smad7 together since cell cycle withdrawal, which is mediated by cyclin D1 suppression, is a prerequisite of differentiation. Therefore, SET mediated repression of cell cycle coupled with Smad7s antagonism of SET at myogenic genes results in a pronounced enhancement of myogenesis. These observations further explain the role of Smad7 in the molecular control of myogenesis, having wider implications for understanding skeletal muscle physiology and pathology.