Repressed expression of the human xanthine oxidoreductase gene. E-box and TATA-like elements restrict ground state transcriptional activity.
Studies were initiated to address the basis for the low xanthine oxidoreductase (XOR) activity in humans relative to nonprimate mammalian species. The expression of the XOR in humans is strikingly lower than in mice, and both transcription rates and core promoter activity of the gene are repressed. Analysis of human XOR promoter activity in hepatocytes and vascular endothelial cells showed that the region from -258 to -1 contains both repressor and activator binding regions regulating core promoter activity. The region between -138 and -1 is necessary and sufficient for initiating, and the region between -258 and -228 is critical for restricting core promoter activity. Within the latter region, site-directed mutations identified a consensus sequence "acacaggtgtgg" (-242 to -230) that contains an E-box that binds a repressor. In addition, the TATA-like element is also required to restrict promoter activity and TFIID binds to this site. The results demonstrate that both an E-box and TATA-like element are required to restrict gene activity. A model is proposed to account for human XOR regulation.
Xu
P
P
Department of Internal Medicine, Division of Respiratory, Critical Care and Occupational Medicine, University of Utah Health Sciences Center and Veterans Affairs Medical Center, Salt Lake City, Utah 84132, USA.
LaVallee
P
P
Hoidal
J R
JR
D020121:5' Untranslated Regions; D000818:Animals; D001667:Binding, Competitive; D002467:Cell Nucleus / Q000201:enzymology; D004730:Endothelium, Vascular / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016385:TATA Box; D014018:Tissue Distribution; D035362:Transcription Factor TFIID; D019473:Transcription Factors, TFII / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000201:enzymology; D014969:Xanthine Oxidase / Q000235:genetics* / Q000378:metabolism*
D020121:5' Untranslated Regions; D035362:Transcription Factor TFIID; D019473:Transcription Factors, TFII; D014969:Xanthine Oxidase