TAZ as a novel enhancer of MyoD-mediated myogenic differentiation

Abstract

Myoblast differentiation is indispensable for skeletal muscle formation and is governed by the precisely coordinated regulation of a series of transcription factors, including MyoD and myogenin, and transcriptional coregulators. TAZ (transcriptional coactivator with PDZ-binding motif) has been characterized as a modulator of mesenchymal stem cell differentiation into osteoblasts and adipocytes through its regulation of lineage-specific master transcription factors. In this study, we investigated whether TAZ affects myoblast differentiation, which is one of the differentiated lineages of mesenchymal stem cells. Ectopic overexpression of TAZ in myoblasts increases myogenic gene expression in a MyoD-dependent manner and hastens myofiber formation, whereas TAZ knockdown delays myogenic differentiation. In addition, enforced coexpression of TAZ and MyoD in fibroblasts accelerates MyoD-induced myogenic differentiation. TAZ physically interacts with MyoD through the WW domain and activates MyoD-dependent gene transcription. TAZ additionally enhances the interaction of MyoD with the myogenin gene promoter. These results strongly suggest that TAZ functions as a novel transcriptional modulator of myogenic differentiation by promoting MyoD-mediated myogenic gene expression. © FASEB.