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Delerive, P. et al.

Delerive, Galardi, Bisi, Nicodeme, Goodwin,

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

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.[1]

References

Identification of liver receptor homolog-1 as a novel regulator of apolipoprotein AI gene transcription. Delerive, P., Galardi, C.M., Bisi, J.E., Nicodeme, E., Goodwin, B. Mol. Endocrinol. (2004) [Pubmed]

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