Structural and Regulatory Analysis of a Cytochrome P450 Gene (CYP2C12) Expressed Predominantly in Female Rat Liver

Cytochrome P450 15β is a female-specific gene product that catalyzes the hydroxylation of steroid sulfates at the 15β position. Isolation and analysis of the gene for rat P450 15β reveals nine coding exons and encompasses more than 35 kb of chromosomal DNA. The intron-exon junctions are at similar positions with the P450 genes of the II family, whose gene structure has been determined. Sequencing of about 2 kb of the 5'-flanking region indicates the presence of the Alu-like R.dre.1 repetitive sequence, a GA-rich stretch that is also found in the 5'-flanking DNA of the male-specific cytochrome P450 16α gene, the enhancer octamer sequence ATGCAAAT, and three CAAAGTT repeats just upstream from the TATA box. Primer extension reveals a major and a minor transcription start site located 22 and 26 bases 5' to the translation initiation codon, respectively. This gene is developmentally regulated and transcriptional activation accounts, at least partly, for the sexually differentiated expression of cytochrome P450 15β.