The human aldehyde dehydrogenase 3 gene (ALDH3): identification of a new exon and diverse mRNA isoforms, and functional analysis of the promoter.

Expression of the human ALDH3 gene is regulated in a tissue-dependent constitutive as well as drug-inducible manner. We identified a new 5'-noncoding exon (exon 1) existing at about 3 kilobase pairs (kb) upstream from the first coding exon (exon 2) of the human ALDH3 gene. Analysis of ALDH3 mRNA revealed the existence of several isoforms with different 5' regions resulting from i) usage of multiple transcriptional initiation sites of the new exon 1, ii) usage of alternative splice acceptor sites at the 3' end of the new intron 1, and iii) alternative splicing out of exon 2. Usage of alternative splice acceptor sites was only found in tissues expressing ALDH3 constitutively, but not in Hep G2 induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Nucleotide sequence analysis and chloramphenicol acetyltransferase (CAT) expression studies showed that a strong promoter region exists at nucleotide (nt) positions -216 to +54 of the gene. Repression activities were found upstream of the -216/+54 region. Several putative drug-inducible elements exist in the regulatory region. A possible regulatory mechanism for tissue-specific constitutive and inducible expression of the human ALDH3 gene is discussed.