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 ho meostasis. We investigated the regulation of this enzyme in the hamste r, a suitable animal model for studying cholesterol metabolism. DNase I hypersensitivity assay revealed the presence of a hypersensitive reg ion in the proximal promoter. Both negative (bile acids, phorbol ester s and insulin) and positive (glucocorticoid hormones) effects were med iated through sequences in the region 318 bp upstream of the ATG codon . All-trans-retinoic acid, cAMP, and LDL did not affect transcriptiona l activity. These findings show that the hamster cholesterol 7 alpha-h ydroxylase gene undergoes a predominant negative regulation, as oppose d to the rat CYP7A homologous gene. (C) 1996 Academic Press, Inc.