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 Sp1 sites, one of which is essential for promoter activity. DNase footprinting has revealed the presence of another region of interaction with nuclear factors (named F2) immediately downstream of the Sp1 sites. This region has been found to be functional since it is capable of stimulating the minimal promoter. The F2 protection is completely and specifically competed by an AP2 consensus oligonucleotide that has been proved to bind AP2alpha exclusively. However, the AP2alpha recombinant protein was unable to bind the F2 region directly, thus suggesting that AP2alpha may participate in F2 protection by protein-protein interactions with other nuclear factors. The minimal promoter has been shown to be stimulated by two additional regions, one located downstream of F2 and the other upstream of the minimal promoter itself. In neuronal cells, the combined stimulatory activities of these three regions have synergistic effects, whereas in non-neuronal cells, there is a negative interference between the upstream and downstream regions. These opposite transcriptional effects may account for at least part of the neuro-specific expression profile of the alpha(3) gene.