Conserved genomic structure of the Cyp1a1 and Cyp1a2 loci and their dioxin responsive elements cluster.

A thorough DNA sequence analysis reveals that the mouse Cyp1a1 and Cyp1a2 loci are located with coding directions opposite to each other. The two genes are separated by approximately 13.9 kb of genomic DNA containing no open reading frames (mCyp1a1_1a2 junction). Within the mCyp1a1_1a2 junction, eight consensus dioxin responsive elements (DREs) are present and seven of the eight DREs located less than 1.4 kb upstream from the Cyp1a1 transcriptional start site. The genomic structure of mouse Cyp1a1 and Cyp1a2 loci is similar to that of human CYP1A1 and CYP1A2 loci. In the human CYP1A1 and CYP1A2 are also arranged in a head to head orientation and separated by a 23 kb genome junction (hCyp1A1_1A2). Comparative sequence analysis between these two genomic junctions demonstrated that the 1.4kb upstream region from the transcriptional start site of mouse Cyp1a1 was highly conserved with that of human CYP1A1. In contrast, there are no conserved DREs in the proximal upstream region of Cyp1a2. The "head to head" genomic structure and position of the DREs cluster region near the Cyp1a1 gene on Cyp1a1_1a2 were confirmed in cattle, dog and rat genome. These results suggest that the conservation of genomic structure of Cyp1a1 and Cyp1a2 genes, and the DREs cluster are important in mammalian biology.