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EMBO reports 3, 12, 1181–1187 (2002)
doi:10.1093/embo-reports/kvf238
Published online: December 2002
Liver receptor homolog 1 controls the expression of the scavenger receptor class B type I
Kristina Schoonjans1, Jean-Sebastien Annicotte1, 5, Thierry Huby2, 5, Oronza A. Botrugno1, Elisabeth Fayard1, Yukihiko Ueda3, John Chapman2 & Johan Auwerx1, 4
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1 Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS/INSERM/Université Louis Pasteur, 67404 Illkirch, France
2 Unité 551 INSERM, Hôpital de la Pitié, 75651 Paris, France
3 Shiga Medical Center Research Institute, 5-4-30 Moriyama, Shiga 524-8524, Japan
4 Institut Clinique de la Souris (ICS), BP 10142, 67404 Illkirch, France
5 J.-S. Annicotte and T. Huby contributed equally to this work
To whom correspondence should be addressed
Kristina Schoonjans Tel: +33 3 8865 3419/3425; Fax: +33 3 8865 3201; schoonja@igbmc.u-strasbg.fr or auwerx@igbmc.u-strasbg.fr
Johan Auwerx Tel: +33 3 8865 3419/3425; Fax: +33 3 8865 3201; schoonja@igbmc.u-strasbg.fr or auwerx@igbmc.u-strasbg.fr
Received 4 June 2002; Accepted 14 October 2002.
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Abstract
The scavenger receptor class B type I (SR-BI), which mediates selective cellular cholesterol uptake from high-density lipoproteins (HDLs), plays a key role in reverse cholesterol transport. The orphan nuclear receptor liver receptor homolog 1 (LRH-1) and SR-BI are co-expressed in liver and ovary, suggesting that LRH-1 might control the expression of SR-BI in these tissues. LRH-1 induces human and mouse SR-BI promoter activity by binding to an LRH-1 response element in the promoter. Retroviral expression of LRH-1 robustly induces SR-BI, an effect associated with histone H3 acetylation on the SR-BI promoter. The decrease in SR-BI mRNA levels in livers of LRH-1+/- animals provides in vivo evidence that LRH-1 regulates SR-BI expression. Our data demonstrate that SR-BI is an LRH-1 target gene and underscore the pivotal role of LRH-1 in reverse cholesterol transport.
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