Transcriptional modulation of mouse mu-opioid receptor distal promoter activity by Sox18.
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 mu-opioid receptor (mor) gene. Here we have identified a positive regulatory element influencing mor 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 mor DP, and did so in a Sox18 concentration-dependent manner. In contrast, overexpression of another Sox member, Sox5, triggered no such trans-activation of mor DP-driven luciferase activity or DNA-protein binding activity. These results suggest that Sox18 directly and specifically stimulates mor gene expression, by trans-activating the mor DP enhancer.
Im
H J
HJ
Department of Pharmacology, The University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church St. S.E., Minneapolis, MN 55455, USA. imh@tc.umn.edu
Smirnov
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D
Yuhi
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Raghavan
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Olsson
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Muscat
G E
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Koopman
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Loh
H H
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D020121:5' Untranslated Regions / Q000235:genetics; D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D016384:Consensus Sequence / Q000235:genetics; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018390:Gene Targeting; D017930:Genes, Reporter; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011499:Protein Processing, Post-Translational; D017450:Receptors, Opioid, mu / Q000235:genetics*; D055760:SOXF Transcription Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*; D014407:Tumor Cells, Cultured
D020121:5' Untranslated Regions; D006609:High Mobility Group Proteins; D016376:Oligonucleotides, Antisense; D017450:Receptors, Opioid, mu; C095473:SOX18 protein, human; D055760:SOXF Transcription Factors; C490653:Sox18 protein, mouse; D014157:Transcription Factors