Abstract
Previously, we reported the presence of dual promoters, referred to as distal (DP) and proximal, with a negative regulatory element between them in the mouse μ-opioid receptor (mor) gene. Here we have identified a positive regulatory element influencingmor DP transcription, which contains multiple consensus binding motifs for Sox factors (sex-determining Sry-like high mobility group box-containing genes). In gel supershift assays, the Sox family 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 morDP, and did so in a Sox18 concentration-dependent manner. In contrast, overexpression of another Sox member, Sox5, triggered no suchtrans-activation of mor DP-driven luciferase activity or DNA-protein binding activity. These results suggest that Sox18 directly and specifically stimulatesmor gene expression, by trans-activating the mor DP enhancer.
Footnotes
- Received January 2, 2000.
- Accepted February 28, 2001.
-
Send reprint requests to: Hee-Jeong Im, Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church St. S.E., Minneapolis, MN 55455. E-mail:imh{at}tc.umn.edu
-
This research was supported by National Institutes of Health Grants DA-00546, DA-01583, DA-05695, KO5-DA-70554, and the A&F Stark Fund of the Minnesota Medical Foundation.
- The American Society for Pharmacology and Experimental Therapeutics
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|