The Class 3 aldehyde dehydrogenase gene (ALDH-3) is differentially expressed. Expression is either constitutive or xenobiotic inducible via an aromatic hydrocarbon (Ah) receptor-mediated pathway, depending upon the tissue. A series of studies were performed to examine the regulation of rat ALDH-3 basal expression. DNase I footprint analysis identified four DNA regions within the proximal 1 kb of the 5' flanking region of rat ALDH-3 which interact with regulatory proteins. Reporter gene and gel mobility shift assays indicate that Sp1-like proteins interact with two proximal DNase I footprinted sites to confer strong promoter activity. Two distal DNase I footprinted sites are found within a region that inhibits rat ALDH-3 promoter activity. This negative region is bound by NF1-like proteins and/or unique proteins. This 1 kb 5' flanking region of rat ALDH-3 may act constitutively in many cell types. In contrast with other Ah receptor regulated genes, no DNA elements or transcription factors acting within this region appear to be involved in regulating xenobiotic-inducible expression of rat ALDH-3.
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