MYOD FUNCTIONS AS A TRANSCRIPTIONAL REPRESSOR IN PROLIFERATING MYOBLASTS

The myogenic basic helix-loop-helix (myo-bHLH) proteins are a family o f transcriptional regulators expressed in myoblasts and differentiated skeletal muscle, Ectopic expression of myo-bHLH regulators transdeter mines some fibroblast cell lines into myoblasts, which exit the cell c ycle and differentiate into skeletal muscle when cultured in low mitog en medium. While members of the myo-bHLH family have been shown to fun ction as transcriptional activators in differentiating muscle, the mol ecular basis of their function in proliferating myoblasts has not been elucidated, In this report, we present evidence that MyoD functions a s a transcriptional repressor in myoblasts, We show that transcription from a cyclin B1 promoter construct is repressed in proliferating myo blasts and that repression is mediated by a pair of MyoD binding sites , We also show that transcription from the cyclin B1 promoter is repre ssed in proliferating C3H10T1/2 cells by ectopic expression of MyoD. T hese results demonstrate that MyoD can repress transcription of specif ic genes in proliferating cells, a novel function that may be importan t to maintenance of the myogenic phenotype and to cell cycle regulatio n in myoblasts.