TBP-like protein (TLP) represses myogenesis via inhibition of the myogenin promoter

Abstract

TBP-like protein (TLP) is one of the metazoan-restricted transcription factors participating in development and differentiation, though the molecular mechanism by which TLP regulates these processes remains unclear. In this study, we investigated the relationship between TLP and myogenesis of mouse C2C12 myoblasts. We found that TLP gene expression decreases during myogenic differentiation. Overexpression and knockdown of TLP revealed that the levels of muscle-specific myosin heavy chain and the myogenic transcription factor myogenin are downregulated by TLP. TLP inhibits the progression of morphological change from myoblasts to myotubes, thereby suppressing myogenesis. We further show that TLP represses the promoter activity of myogenin. The proximal AT-rich sequence of the myogenin promoter is responsible for TLP-mediated transcriptional repression. The results of this study suggest that TLP inhibits myogenesis through downregulation of the myogenin gene.

Keywords: Myogenesis; Myogenin; TFIIA; TLP; TRF2.