Liver receptor homolog 1 controls the expression of the scavenger receptor class B type I.
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.
Schoonjans
Kristina
K
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, 67404 Illkirch, France. schoonja@igbmc.u-strasbg.fr
Annicotte
Jean-Sebastien
JS
Huby
Thierry
T
Botrugno
Oronza A
OA
Fayard
Elisabeth
E
Ueda
Yukihiko
Y
Chapman
John
J
Auwerx
Johan
J
D000818:Animals; D001665:Binding Sites; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D010053:Ovary / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D018955:CD36 Antigens; D008565:Membrane Proteins; C431936:Nr5a2 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B