Regulation of the hamster cholesterol 7 alpha-hydroxylase gene (CYP7A): prevalence of negative over positive transcriptional control.

Cholesterol 7 alpha-hydroxylase plays a crucial role in cholesterol homeostasis. We investigated the regulation of this enzyme in the hamster, a suitable animal model for studying cholesterol metabolism. DNase I hypersensitivity assay revealed the presence of a hypersensitive region in the proximal promoter. Both negative (bile acids, phorbol esters and insulin) and positive (glucocorticoid hormones) effects were mediated through sequences in the region 318 bp upstream of the ATG codon. All-trans-retinoic acid, cAMP, and LDL did not affect transcriptional activity. These findings show that the hamster cholesterol 7 alpha-hydroxylase gene undergoes a predominant negative regulation, as opposed to the rat CYP7A homologous gene.