Structural organization of the human gastrointestinal glutathione peroxidase (GPX2) promoter and 3'-nontranscribed region: transcriptional response to exogenous redox agents.
The flanking upstream and downstream regions of the human GPX270%). The human GPX2 promoter region was not G-C rich (<50% G+C) and classical TATA/CCAAT elements were not present. The ubiquitous SP1 and AP elements were present. Several GATA elements as well as liver-specific sites (HNF series) were present. Despite the unique intestinal specific expression of GPX2, classical intestine-specific sites were not detected in the flanking 5' or 3' regions. The ability of the GPX2 promoter to direct transcription was confirmed. Exogenous agents capable of producing oxidative stress, such as paraquat, could induce the transcriptional activity of the GPX2 promoter. Analysis of three previously reported polymorphism sites revealed that they represented the most common polymorphisms. Surprisingly, the human GPX2 promoter could direct transcription and respond to oxidative stress in the murine NIH3T3 fibroblast cell line, which is devoid of the ability to bind to a variety of intestinal specific elements. This finding suggests that the unique intestinal specific expression of GPX2 may be due to elements in the intron, the flanking 3'-nontranslated region, or to elements existing even farther upstream. The ability of GPX2 to respond transcriptionally to redox stress is likely to be more physiologically relevant than post-transcriptional regulation which is dependent upon selenium availability.
Kelner
M J
MJ
Department of Pathology, University of California, 200 West Arbor Drive, San Diego, CA 92103-8320, USA. mkelner@ucsd.edu
Bagnell
R D
RD
Montoya
M A
MA
Lanham
K A
KA
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000235:genetics*; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D011993:Recombinant Fusion Proteins; D004247:DNA; C117436:GPX2 protein, human; C492172:Gpx2 protein, mouse; D005979:Glutathione Peroxidase; D008156:Luciferases; D010269:Paraquat