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Functional analysis of the rat bile salt export pump gene promoter

Gerloff, Thomas and Geier, Andreas and Roots, Ivar and Meier, Peter J. and Gartung, Carsten. (2002) Functional analysis of the rat bile salt export pump gene promoter. European journal of biochemistry, Vol. 244, H. 1. S. 39-44.

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Official URL: http://edoc.unibas.ch/dok/A5261633

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Abstract

The 5' flanking region of the bile salt export pump (Bsep) gene was systematically analysed to provide the basis for understanding the mechanisms which regulate Bsep transcription. In addition substrates and drugs were investigated for their ability to alter Bsep promoter activity. Bsep promoter function was restricted to hepatocyte derived HepG2 cells. The 5' deletional analysis revealed a biphasic shape of reporter gene activities, indicating a suppressive element between nucleotides -800 and -512. Two consensus sites for the farnesoid X receptor (FXR) were located at nucleotides -473 and -64. The latter was characterized as functionally active in bile acid-mediated feed-back regulation of Bsep transcription. Bsep promoter activity was reduced by rifampin and beta-estradiol. The anti-estrogen tamoxifen stimulated promoter activity. Dexamethasone, hydrocortisone and phenobarbital had no effect on Bsep promoter activity. In conclusion, the data suggest that transcriptional regulation of the Bsep gene can be modulated by a number of endogenous compounds and xenobiotics. FXR was a major regulatory factor, mediating bile acid feed-back stimulation of Bsep transcription.
Faculties and Departments:11 Rektorat und Verwaltung > Vizerektorat Forschung
UniBasel Contributors:Meier-Abt, Peter J.
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:BlackwellVol. 269
ISSN:0014-2956
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:23
Deposited On:22 Mar 2012 13:34

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