Autoactivation of Xenopus MyoD transcription and its inhibition by USF

Members of the MyoD family of muscle-specific transcription factors play central roles in the formation and differentiation of skeletal muscle; however, steps involved in the initiation and subsequent regulation of myogenic factor expression are poorly understood. To investigate mechanisms underlying muscle cell type-specific MyoD gene expression, the functions of regulatory elements that control Xenopus MyoDa gene transcription were analyzed. We show that E boxes in the XMyoDa promoter have dual functions. These sites bind myogenic basic helix-loop-helix proteins and serve as target sites for direct autoactivation. In addition, these regulatory elements bind other, more widely expressed proteins that repress promoter activity. In particular, the binding of the transcriptional regulatory protein USF to a conserved site in the XMyoDa promoter decreased basal activity of the promoter and inhibited MyoD-dependent autoactivation. The results suggest that XMyoD transcription and myogenic factor activity is governed by a competition between muscle-specific, positive-acting factors and widely expressed repressors for binding to common regulatory sites.