The minimal promoter of the human alpha(3) nicotinic receptor subunit gene- Molecular and functional characterization

The minimal promoter of the human alpha (3) nicotinic receptor subunit gene has been mapped to a region of 60 base pairs and found to contain two Spl sites, one of which is essential for promoter activity, DNase footprinting has revealed the presence of another region of interaction with nuclear fac tors (named F2) immediately downstream of the Spl sites. This region has be en found to be functional since it is capable of stimulating the minimal pr omoter. The F2 protection is completely and specifically competed by an AP2 consensus oligonucleotide that has been proved to bind AP2 alpha exclusive ly. However, the AP2 alpha recombinant protein was unable to bind the F2 re gion directly, thus suggesting that AP2 alpha may participate in F2 protect ion by protein-protein interactions with other nuclear factors, The minimal promoter has been shown to be stimulated by two additional regions, one lo cated downstream of F2 and the other upstream of the minimal promoter itsel f. In neuronal cells, the combined stimulatory activities of these three re gions have synergistic effects, whereas in nonneuronal cells, there is a ne gative interference between the upstream and downstream regions, These oppo site transcriptional effects may account for at least part of the neuro-spe cific expression profile of the alpha (3) gene.