Activity of the nicotinic acetylcholine receptor alpha 5 and alpha 7 subunit promoters in muscle cells

The acetylcholine receptor alpha5 and alpha7 subunits are components of dif ferent nicotinic receptor subtypes expressed in the nervous system. However , they are also present in non-neuronal tissues. We have detected alpha5 an d alpha7 transcripts in mouse C2C12 muscle cells. Moreover, on differentiat ion of myoblasts into myotubes, the amount of alpha7 transcripts increased significantly, whereas alpha5 remained unchanged. In order to explore how t he expression of these neuronal genes is regulated in muscle, we have chara cterized their promoter activities. Deletion and mutagenesis analysis with transfected reporter genes showed that transcriptional activity was control led by regulatory elements also operative in neuronal-like cells. Thus, the activity of the alpha5 subunit core promoter decreased to similar to 50% o n alteration of one, two, or three of the five Sp1 binding sites present in this region and was almost abolished when four or five sites were mutated simultaneously. In the case of the alpha7 subunit promoter, the upstream st imulatory factor and the early growth response gene transcription factor we re involved in regulating its transcriptional activity. In addition, the al pha7 promoter was activated during the differentiation process, in a mechan ism partially dependent on the mentioned factors.