Regulation of human sterol 27-hydroxylase gene (CYP27A1) by bile acids and hepatocyte nuclear factor 4 alpha (HNF4 alpha)
rat; liver; bile acid synthesis; down-regulation; hepatocytes; nuclear receptor; transcriptional regulation; negative feedback-regulation; Genetics & Heredity; cholesterol 7-alpha-hydroxylase; cholic-acid; farnesoid X receptor; heterodimer partner; x-receptor; small; alpha-fetoprotein transcription factor; cerebrotendinous xanthomatosis; factor 4-alpha
Mitochondrial sterol 27-hydroxylase (CYP27Al) catalyses sterol side-chain oxidation of bile acid synthesis front cholesterol, and the first reaction of the acidic bile acid biosynthetic pathway. Hydrophobic bile acids suppress human CYP27Al gene reporter activity when assayed in human hepatocellular blastoma HepG2 cells. Bile acids also inhibit CYP27Al reporter activity in human embryonic kidney 293 cells. A putative bile acid response element (BARE) was mapped to a region downstream of nt - 147 of the human CYP27Al gene, within which a binding site for a liver-specific nuclear receptor, HNF4alpha, is identified. HNF4alpha strongly stimulates CYP27Al gene transcription and mutation of its binding site markedly reduced promoter activity. Results suggest that human CYP27Al gene transcription is suppressed by bile acids and HNF4alpha plays a pivotal role in transcriptional regulation of this gene. (C) 2003 Elsevier Science B.V. All rights reserved.
Chen W L; Chiang J Y L
Gene
2003
2003-08
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/s0378-1119(03)00631-0" target="_blank" rel="noreferrer noopener">10.1016/s0378-1119(03)00631-0</a>
Molecular mechanisms of nuclear receptor regulation of bile acid synthesis
transactivation; feedback-regulation; identification; cholesterol 7-alpha-hydroxylase; transcription; heterodimer partner; repression; shp; factor 4-alpha; 7-alpha-hydroxylase gene cyp7a1
Chiang J Y L; Zhang M; Chen W; Norlin M; Owsley E
2003
2003
Book/Monograph
n/a