Organization and characterization of the rat class 3 aldehyde dehydrogenase gene

Expression of class 3 aldehyde dehydrogenase (ALDH-3) is constitutive or inducible, depending on the tissue. ALDH-3 induction occurs both during neoplastic development and after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to study the regulation of ALDH-3 gene expression, ALDH-3 genomic sequences have been obtained from normal rat genomic DNA. Two overlapping genomic fragments (ALDH-UTR-1 and ALDH-NL2) contain the entire ALDH-3 gene along with considerable 5'- and 3'-flanking sequences. The rat ALDH-3 gene spans approximately 9 kilobases in length and consists of eleven exons; ten coding and one 5'-noncoding. The region 5' to exon one contains several putative transcription factor binding elements which may be important in the TCDD inducibility of this gene. These include a xenobiotic response element (XRE), a drug response element (DRE), LAP and Ap1 binding sites, and one Sp1 site. There are considerable differences in organization between the rat and human class 3 ALDH genes. Primer extension and RNase protection analysis indicate that both basal and TCDD-inducible expression of the ALDH-3 gene utilize the same multiple transcription start sites.