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

被引:75
作者
Delerive, P
Galardi, CM
Bisi, JE
Nicodeme, E
Goodwin, B
机构
[1] GlaxoSmithKline Res & Dev Ltd, Cardiovasc & Urogenital Dis Ctr Excellence Drug D, F-91951 Les Ulis, France
[2] GlaxoSmithKline, High Throughput Biol, Res Triangle Pk, NC 27709 USA
[3] GlaxoSmithKline, Gene Interference Grp, Res Triangle Pk, NC 27709 USA
关键词
D O I
10.1210/me.2004-0132
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:2378 / 2387
页数:10
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