Promoter specificity mediates the independent regulation of neighboring genes.

Although enhancers can exert their influence over great distances, their effect is generally limited to a single gene. To discern the mechanism by which this constraint can he mediated, we have studied three neighboring Drosophila genes: decapentaplegic (dpp), SLY1 homologous (Slh) and out at first (oaf). Several dpp enhancers are positioned close to Slh and oaf, and yet these genes are unaffected by the dpp elements. However, when a transposon is located within the oaf gene, the dpp enhancers activate the more distant transposon promoters while still ignoring the closer Slh and oaf start sites. To test whether this promoter specificity accounts for the regulatory autonomy normally found for the three genes, we used in vivo gene targeting to replace the oaf promoter with a dpp-compatible one in an otherwise normal chromosome. Strikingly, this chimeric gene is now activated by the dpp enhancers. Thus, the properties of the promoters themselves are sufficient to mediate the autonomous regulation of genes in this region.