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Mol Endocrinol. 2004 Oct;18(10):2378-87. Epub 2004 Jun 24.

Identification of liver receptor homolog-1 as a novel regulator of apolipoprotein AI gene transcription.

Author information

1
GlaxoSmithKline, Cardiovascular & Urogenital Center of Excellence for Drug Discovery, 91951 Les Ulis, France. pxd14884@gsk.com <pxd14884@gsk.com>

Abstract

The orphan nuclear receptor liver receptor homolog-1 (LRH-1) has been reported to play a role in bile acid biosynthesis and reverse cholesterol transport. In this study, we examined the role of LRH-1 in the regulation of the apolipoprotein AI (APOAI) gene. Using RNA interference and adenovirus-mediated overexpression, we show that LRH-1 directly regulates APOAI gene transcription. Transient transfection experiments and EMSAs revealed that LRH-1 directly regulates APOAI transcription by binding to an LRH-1 response element located in the proximal APOAI promoter region. Chromatin immunoprecipitation experiments revealed that LRH-1 binds to the human APO AI promoter in vivo. Finally, we show that the transcriptional repressor SHP (small heterodimer partner) suppressed APOAI gene expression by inhibiting LRH-1 transcriptional activity. Taken together, our results demonstrate that LRH-1 is a novel regulator of APOAI transcription and underscore the role of this receptor in cholesterol homeostasis.

PMID:
15218078
DOI:
10.1210/me.2004-0132
[Indexed for MEDLINE]

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