ISOLATION OF A PROMOTER REGION IN MOUSE CYTOCHROME-P450 3A (CYP3A16) GENE AND ITS TRANSCRIPTIONAL CONTROL

An 11.5 kb fragment of the mouse Cyp3a16 gene containing the 5' flanki ng region was isolated from the lambda DASHII mouse genomic library. A part of the 5' flanking region and the first exon of Cyp3a16 gene wer e sequenced. S1 mapping analysis showed the presence of two transcript ional initiation sites. The first exon was completely identical to Cyp 3a16 cDNA. The identity of 5' flanking sequences between Cyp3a16 and C yp3a11 genes was about 69%. A typical TATA box and a basic transcripti on element (BTE) were found as seen with other CYP3A genes from variou s animal species. Moreover, some putative transcriptional regulatory e lements were also found in addition to the sequence motif seen for the formation of Z-type DNA. To examine the transcriptional activity of C yp3a11 gene, DNA fragments in the 5'-flanking region of the gene were inserted front of the luciferase structural gene, and the constructs w ere transfected in primary hepatocytes. The analysis of the luciferase activity indicated that the region between -146 and -56 was necessary for the transcription of CYP3a16 gene.