An overlapping binding site in the CYP7A1 promoter allows activation of FXR to override the stimulation by LXRalpha.

An overlapping binding site in the CYP7A1 promoter allows activation of FXR to override the stimulation by LXRalpha. Research Abstract Details 

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An overlapping binding site in the CYP7A1 promoter allows activation of FXR to override the stimulation by LXRalpha. Abstract Text:

Quan Shang,Luxing Pan,Monica Saumoy,John Y L Chiang,G Stephen Tint,Gerald Salen,Guorong Xu,Quan Shang,Luxing Pan,Monica Saumoy,John Y L Chiang,G Stephen Tint,Gerald Salen,Guorong Xu,

The aim of this study was to explore why in rabbits activation of farnesoid X receptor (FXR) is dominant over activated liver X receptor-alpha (LXRalpha) in the regulation of CYP7A1. We cloned the rabbit CYP7A1 promoter and found a fetoprotein transcription factor (FTF) binding element embedded within the LXRalpha binding site (LXRE). Gel shift assays demonstrated that FTF competes with LXRalpha for binding to LXRE. Short heterodimer partner (SHP) enhances the competitive ability of FTF. Studies in HepG2 cells showed that SHP combined with FTF had more powerful effect to offset the stimulation of CYP7A1 by LXRalpha. Gel shift and chromatin immunoprecipitation assays demonstrated that SHP with FTF diminished LXRalpha binding to the CYP7A1 promoter. In vivo studies in rabbits fed cholesterol for 10 days showed that hepatic expression of SHP but not FTF rose and LXRalpha-bound LXRE decreased. We propose that the SHP/FTF heterodimer occupies LXRE via the embedded FTF binding element and blocks LXRalpha from recruiting to LXRE. Therefore, activation of FXR, which upregulates SHP expression, will eliminate the stimulatory effect of LXRalpha on the CYP7A1 promoter because increased levels of SHP combined with FTF diminish the recruitment of LXRalpha to CYP7A1 promoter.

An overlapping binding site in the CYP7A1 promoter allows activation of FXR to override the stimulation by LXRalpha. Publishing Authors By Initials

Q Shang,L Pan,M Saumoy,JY Chiang,GS Tint,G Salen,G Xu,Q Shang,L Pan,M Saumoy,JY Chiang,GS Tint,G Salen,G Xu,

For similar proteins: transcription factors research abstracts see: proteins: transcription factors research

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An overlapping binding site in the CYP7A1 promoter allows activation of FXR to override the stimulation by LXRalpha. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: American journal of physiology. Gastrointestinal a

VOLUME: 293

Page Numbers: G817-23

Journal Abbreviation: Am. J. Physiol. Gastrointest.

ISSN: 0193-1857

DAY: 9

MONTH: 08

YEAR: 2007

An overlapping binding site in the CYP7A1 promoter allows activation of FXR to override the stimulation by LXRalpha. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100901227

An overlapping binding site in the CYP7A1 promoter allows activation of FXR to override the stimulation by LXRalpha. Keywords Mesh Terms:

KEYWORDS: Transcription Factors

MESH TERMS: genetics

Chemical & Substance for Abstract: An overlapping binding site in the CYP7A1 promoter allows activation of FXR to override the stimulation by LXRalpha. Information

Substance Name: Cholesterol 7-alpha-Hydroxylase

Registry Number: EC 1.14.13.17

Grant and Affiliation Information for An overlapping binding site in the CYP7A1 promoter allows activation of FXR to override the stimulation by LXRalpha.

AFFILIATION: Department of Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: DK-58379

ACRONYM: DK

MEDLINETA: Am J Physiol Gastrointest Live

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