MYOGENIN AND ACETYLCHOLINE-RECEPTOR ALPHA-GENE PROMOTERS MEDIATE TRANSCRIPTIONAL REGULATION IN RESPONSE TO MOTOR INNERVATION

Several genes expressed in skeletal muscle are transcriptionally repre ssed by electrical activity arising from motor innervation and are rap idly induced following denervation. Among these are genes encoding the subunits of the nicotinic acetylcholine receptor (AChR) and the myoge nic helix-loop-helix protein myogenin, which activates muscle-specific genes. To understand how electrical activity arising from motor inner vation is converted into a transcriptional response, we have attempted to localize cis-acting sequences in the AChR alpha subunit and myogen in genes sufficient to direct activity-dependent transcription. Here w e show that an 111-base pair and a 335-base pair region from the promo ters of the AChR alpha subunit and myogenin genes, respectively, can c onfer activity-dependent regulation to a linked reporter gene in trans genic mice. The presence of binding sites for myogenic helix-loop-heli x 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 change s in gene transcription in skeletal muscle.