Transcriptional activation of the cholesterol 7 alpha-hydroxylase gene (CYP7A) by nuclear hormone receptors

Title

Transcriptional activation of the cholesterol 7 alpha-hydroxylase gene (CYP7A) by nuclear hormone receptors

Creator

Crestani M; Sadeghpour A; Stroup D; Galli G; Chiang J Y L

Publisher

Journal of Lipid Research

Date

1998
1998-11

Description

The gene encoding cholesterol 7 alpha-hydroxylase (CYP7A), the rate-limiting enzyme in bile acid synthesis, is transcriptionally regulated by bile acids and hormones. Previously, we have identified two bile acid response elements (BARE) in the promoter of the CYP7A gene, The BARE II is located in nt -149/-118 region and contains three hormone response element (HRE)-like sequences that form two overlapping nuclear receptor binding sites. One is a direct repeat separated by one nucleotide DR1 (-146-TGGACTtAGTTCA-134) and the other is a direct repeat separated by five nucleotides DR5 (-139-AGTTCAaggccGGG TAA-123). Mutagenesis of these HRE sequences resulted in lower transcriptional activity of the CYP7A promoter/reporter genes in transient transfection assay in HepG2 cells. The orphan nuclear receptor, hepatocyte nuclear factor 4 (HNF-4)(1), binds to the DR1 sequence as assessed by electrophoretic mobility shift assay, and activates the CYP7A promoter/reporter activity by about 9-fold. Cotransfection of HNF-4 plasmid with another orphan nuclear receptor, chicken ovalbumin upstream promoter-transcription factor LI (COUP-TRI), synergistically activated the CYP7A transcription by 80-fold. The DR5 binds the RXR/RAR heterodimer, A hepatocyte nuclear factor-3 (HNF-3) binding site (-175-TGTTTGTTCT-166) was identified. HNF-3 was required for both basal transcriptional activity and stimulation of the rat CYP7A promoter activity by retinoic acid, Combinatorial interactions and binding of these transcription factors to BAREs may modulate the promoter activity and also mediate bile acid repression of CYP7A gene transcription.

Subject

rat; liver; bile acid synthesis; Biochemistry & Molecular Biology; expression; messenger-rna; elements; metabolism; promoter; nuclear; mutations; cytochrome P450; cholesterol 7; alpha-hydroxylase; bile acid response element; factor coup-tf; gene transcription and regulation; hormone receptor; retinoic acid receptors

Identifier

n/a

Format

Journal Article or Conference Abstract Publication

URL Address

n/a

Search for Full-text

Users with a NEOMED Library login can search for full-text journal articles at the following url: https://libraryguides.neomed.edu/home

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

2192-2200

Issue

11

Volume

39

Citation

Crestani M; Sadeghpour A; Stroup D; Galli G; Chiang J Y L, “Transcriptional activation of the cholesterol 7 alpha-hydroxylase gene (CYP7A) by nuclear hormone receptors,” NEOMED Bibliography Database, accessed July 25, 2021, https://neomed.omeka.net/items/show/8998.

Social Bookmarking