Regulation of human sterol 27-hydroxylase gene (CYP27A1) by bile acids and hepatocyte nuclear factor 4alpha (HNF4alpha).

Title

Regulation of human sterol 27-hydroxylase gene (CYP27A1) by bile acids and hepatocyte nuclear factor 4alpha (HNF4alpha).

Creator

Chen Wenling; Chiang John Y L

Publisher

Gene

Date

2003
2003-08

Description

Mitochondrial sterol 27-hydroxylase (CYP27A1) catalyses sterol side-chain oxidation of bile acid synthesis from cholesterol, and the first reaction of the acidic bile acid biosynthetic pathway. Hydrophobic bile acids suppress human CYP27A1 gene reporter activity when assayed in human hepatocellular blastoma HepG2 cells. Bile acids also inhibit CYP27A1 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 CYP27A1 gene, within which a binding site for a liver-specific nuclear receptor, HNF4alpha, is identified. HNF4alpha strongly stimulates CYP27A1 gene transcription and mutation of its binding site markedly reduced promoter activity. Results suggest that human CYP27A1 gene transcription is suppressed by bile acids and HNF4alpha plays a pivotal role in transcriptional regulation of this gene.

Subject

Humans; Cell Line; Transfection; Gene Expression Regulation/drug effects; Base Sequence; Binding Sites/genetics; Response Elements/genetics; Molecular Sequence Data; Mutation; Chenodeoxycholic Acid/pharmacology; Transcription Factors/genetics/*metabolism; Hepatocyte Nuclear Factor 4; Mutagenesis; *DNA-Binding Proteins; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Bile Acids and Salts/*pharmacology; Cholestanetriol 26-Monooxygenase; DNA/chemistry/genetics; Luciferases/genetics/metabolism; Phosphoproteins/genetics/*metabolism; Recombinant Fusion Proteins/genetics/metabolism; Steroid Hydroxylases/*genetics; DNA; Dose-Response Relationship; Drug; Cultured; Receptors; Tumor Cells; Cloning; Molecular; Sequence Analysis; Promoter Regions; Genetic/*genetics; Cytoplasmic and Nuclear/genetics/metabolism; Site-Directed

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

71–82

Volume

313

Citation

Chen Wenling; Chiang John Y L, “Regulation of human sterol 27-hydroxylase gene (CYP27A1) by bile acids and hepatocyte nuclear factor 4alpha (HNF4alpha).,” NEOMED Bibliography Database, accessed June 23, 2021, https://neomed.omeka.net/items/show/5341.

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