Structure of the Rat Gene Encoding Cholesterol 7 α-Hydroxylase

Cholesterol 7α-hydroxylase (7α-hydroxylase) is a microsomal cytochrome P-450 that catalyzes the first and ratelimiting step in bile acid biosynthesis, the major catabolic pathway in cholesterol homeostasis. The gene encoding the rat 7α-hydroxylase has been isolated and characterized. Southern blotting experiments demonstrated that the gene is present in a single copy in the rat genome. DNA sequence analysis showed that the 7α-hydroxylase gene is unique among the characterized cytochrome P-450s in that it contains only six exons. Nuclease S1 and primer-extension mapping experiments positioned the 5′-ends of the 7α-hydroxylase mRNA approximately 20-25 nucleotides downstream of a consensus TATAAA sequence. RNA blotting experiments demonstrated the presence of multiple 7α-hydroxylase mRNAs that differ in the lengths of their 3′-untranslated regions.