Myogenin and acetylcholine receptor alpha gene promoters mediate transcriptional regulation in response to motor innervation

Abstract

Several genes expressed in skeletal muscle are transcriptionally repressed by electrical activity arising from motor innervation and are rapidly induced following denervation. Among these are genes encoding the subunits of the nicotinic acetylcholine receptor (AChR) and the myogenic helix-loop-helix protein myogenin, which activates muscle-specific genes. To understand how electrical activity arising from motor innervation is converted into a transcriptional response, we have attempted to localize cis-acting sequences in the AChR alpha subunit and myogenin genes sufficient to direct activity-dependent transcription. Here we show that an 111-base pair and a 335-base pair region from the promoters of the AChR alpha subunit and myogenin genes, respectively, can confer activity-dependent regulation to a linked reporter gene in transgenic mice. The presence of binding sites for myogenic helix-loop-helix proteins in both of these regulatory regions is consistent with the hypothesis that these myogenic regulators serve as nuclear targets for the signaling cascade through which motor innervation leads to changes in gene transcription in skeletal muscle.