HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M500449-JLR200v1 47/5/997    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shang, Q. Articles by Xu, G. Search for Related Content PubMed PubMed Citation Articles by Shang, Q. Articles by Xu, G. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 47, 997-1004, May 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

The stimulatory effect of LXR is blocked by SHP despite the presence of a LXR binding site in the rabbit CYP7A1 promoter

Quan Shang^1,*, Luxing Pan^1,, Monica Saumoy^*, John Y. L. Chiang, G. Stephen Tint^*,, Gerald Salen^* and Guorong Xu^2,*,

^* Department of Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103
Medical Research Service, Department of Veterans Affairs Medical Center, East Orange, NJ 07018
Department of Biochemistry and Molecular Pathology, Northeastern Ohio University College of Medicine, Rootstown, OH 44272

Published, JLR Papers in Press, February 17, 2006.

¹ Q. Shang and L. Pan contributed equally to this work.

² To whom correspondence should be addressed. e-mail: xugu{at}umdnj.edu

The transcription of the cholesterol 7-hydroxylase gene (CYP7A1) is greatly decreased in cholesterol-fed rabbits. To determine whether the molecular structure of the promoter is responsible for this downregulation, we cloned the rabbit CYP7A1 promoter, identified the binding sites for -fetoprotein transcription factor (FTF) and liver X receptor (LXR), and studied the effects of FTF, LXR, and SHP on its transcription. Adding LXR/retinoid X receptor together with their ligands (L/R) to the promoter/reporter construct transfected into HepG2 cells greatly increased its activity. FTF did not increase promoter activity, nor did it enhance the stimulatory effect of L/R. Mutating the FTF binding site abolished the promoter baseline activity. Increasing amounts of SHP abolished the effect of L/R, and FTF enhanced the ability of SHP to decrease promoter activity below baseline levels. Thus, downregulation of CYP7A1 in cholesterol-fed rabbits is attributable secondarily to the activation of farnesoid X receptor, which increases SHP expression to override the positive effects of LXR. Although FTF is a competent factor for maintaining baseline activity, it does not further enhance and may suppress CYP7A1 transcription.

Supplementary key words farnesoid X receptor • liver X receptor • -fetoprotein transcription factor • SHP • dietary cholesterol • cholesterol 7-hydroxylase

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Q. Shang, L. Pan, M. Saumoy, J. Y. L. Chiang, G. S. Tint, G. Salen, and G. Xu An overlapping binding site in the CYP7A1 promoter allows activation of FXR to override the stimulation by LXR{alpha} Am J Physiol Gastrointest Liver Physiol, October 1, 2007; 293(4): G817 - G823. [Abstract] [Full Text] [PDF]