Hepatocyte nuclear factor 1 binds to and transactivates the human but not the rat CYP7A1 promoter

Cholesterol 7 alpha-hydroxylase (CYP7A1), a liver-specific enzyme, catalyze s the rate-limiting step in the degradation pathway of cholesterol to bile acids, and thus plays a key role in cholesterol homeostasis. To elucidate t he mechanisms that control hepatic expression of the human CYP7A1 gene, we are studying the promoter region. Initially, we observed that up to 40% of the overall transcriptional activity of the promoter in HepG2 cells was ass ociated with DNA sequences from -65 to -1 of the human gene. Within this re gion, a binding site for the liver-enriched transcription factor HNF-1 (-56 to -49) has been identified. Binding of HNF-1 to this site leads to transc riptional activation of the human promoter. The corresponding segment from the rat CYP7A1 gene does not bind HNF-1; instead, it is bound by the orphan receptors ARP-1 (COUP-TFII) and LXR alpha, that are implicated in dietary regulation. (C) 1999 Academic Press.