MOLECULAR CHARACTERIZATION OF THE MURINE AHR GENE - ORGANIZATION, PROMOTER ANALYSIS, AND CHROMOSOMAL ASSIGNMENT

The AH receptor is a ligand-activated transcription factor that mediat es the biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin. The AH receptor has primary sequence homology to its dimerization partner the AH receptor nuclear translocator, and to the Drosophila proteins S im and Per. Characterization of the gene encoding the murine AH recept or (Ahr gene) reveals that its structural organization is also conserv ed with respect to the sim gene, since 6 of 11 Ahr exons are spliced a t homologous sites. Interestingly, little splicing homology was observ ed between the Ahr and per genes. The promoter of the Ahr gene is GC-r ich and contains no TATA or CCAAT boxes; however, sequence analysis ha s shown several binding sites for the transcription factor Sp1 (GC box es). Additionally we have identified a potential cAMP response element , AP-1 and E box sites, and two elements demonstrated in other genes t o confer placenta-specific expression. Using a restriction fragment le ngth polymorphism in exon 7 and recombinant inbred mouse lines, the Ah r gene was found to be concordant with the phenotypically defined Ahr locus, supporting the identity of these two genetic elements.