Identification of a bile acid response element in the cholesterol 7 alpha-hydroxylase gene CYP7A.

Title

Identification of a bile acid response element in the cholesterol 7 alpha-hydroxylase gene CYP7A.

Creator

Stroup D; Crestani M; Chiang J Y

Publisher

The American journal of physiology

Date

1997
1997-08

Description

The transcriptional activity of the cholesterol 7 alpha-hydroxylase gene CYP7A is repressed by bile acids. Taurine conjugates of chenodeoxycholate and deoxycholate, but not cholate and ursodeoxycholate, inhibited the CYP7A promoter/luciferase reporter activity in transient transfection assays in Hep G2 cells. A region from nucleotide (nt) -74 to -55 was found to mediate bile acid response. However, deletion of this bile acid response element (BARE-I) enhanced reporter activity but did not eliminate the bile acid response. This is due to the presence of another BARE-II located in a conserved region between nt -149 and -128. Deletion or mutations of these sequences reduced promoter activity and abolished bile acid repression. This BARE-II shares an identical AGTTCAAG core sequence with BARE-I. Electrophoretic mobility shift assays of BARE-I and BARE-II probes using Hep G2 nuclear extract and the partially purified binding activity of nt -65/-54 DNA-affinity column revealed that the same or a similar nuclear protein might bind to both BAREs. BARE-II is the major BARE involved in the transcriptional repression of the CYP7A gene by hydrophobic bile acids.

Subject

Animals; Base Sequence; Bile Acids and Salts/*pharmacology; Cholesterol 7-alpha-Hydroxylase/*genetics; Cultured; DNA-Binding Proteins/metabolism; Feedback; Genes; Genes/*drug effects; Luciferases/genetics; Rats; Reporter; Tumor Cells

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

G508–517

Issue

2

Volume

273

Citation

Stroup D; Crestani M; Chiang J Y, “Identification of a bile acid response element in the cholesterol 7 alpha-hydroxylase gene CYP7A.,” NEOMED Bibliography Database, accessed October 28, 2021, https://neomed.omeka.net/items/show/4591.

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