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.
De Fabiani
E
E
Istituto di Scienze Farmacologiche, Universit degli Studi di Milano, Italy.
Crestani
M
M
Marrapodi
M
M
Pinelli
A
A
Chiang
J Y
JY
Galli
G
G
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000096:biosynthesis / Q000235:genetics*; D003062:Codon; D016384:Consensus Sequence; D006224:Cricetinae; D000242:Cyclic AMP / Q000494:pharmacology; D003850:Deoxyribonuclease I; D003907:Dexamethasone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D008156:Luciferases / Q000096:biosynthesis; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D013154:Spleen / Q000201:enzymology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003062:Codon; D007328:Insulin; D008077:Lipoproteins, LDL; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D014212:Tretinoin; D003907:Dexamethasone; D002784:Cholesterol; D000242:Cyclic AMP; D008156:Luciferases; D002790:Cholesterol 7-alpha-Hydroxylase; D003850:Deoxyribonuclease I