Transcriptional modulation of mouse mu-opioid receptor distal promoter activity by Sox18

Previously, we reported the presence of dual promoters, referred to as dist al (DP) and proximal, with a negative regulatory element between them in th e mouse mu -opioid receptor (mor) gene. Here we have identified a positive regulatory element influencing mor DP transcription, which contains multipl e consensus binding motifs for Sox factors (sex-determining Sry-like high m obility group box-containing genes). In gel supershift assays, the Sox fami ly member Sox18 bound directly to the multiple Sox consensus binding motifs of the mor DP enhancer. Overexpression of Sox18 cDNA increased luciferase activity regulated by the mor DP, and did so in a Sox18 concentration-depen dent manner. In contrast, overexpression of another Sox member, Sox5, trigg ered no such trans-activation of mor DP-driven luciferase activity or DNA-p rotein binding activity. These results suggest that Sox18 directly and spec ifically stimulates mor gene expression, by trans-activating the mor DP enh ancer.