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KMID : 0624620150480090513
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BMB Reports
2015 Volume.48 No. 9 p.513 ~ p.518
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Transcriptional regulation of Niemann-Pick C1-like 1 gene by liver receptor homolog-1
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Lee Eui-Sup
Seo Hyun-Jung
Back Su-Sun
Han Seung-Ho
Jeong Yeon-Ji
Lee Jin-Wook
Choi Soo-Young
Han Kyu-Hyung
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Abstract
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Factors that modulate cholesterol levels have major impacts on cardiovascular disease. Niemann-Pick C1-like 1 (NPC1L1) functions as a sterol transporter mediating intestinal cholesterol absorption and counter-balancing hepatobiliary cholesterol excretion. The liver receptor homolog 1 (LRH-1) had been shown to regulate genes involved in hepatic lipid metabolism and reverse cholesterol transport. To study whether human NPC1L1 gene is regulated transcriptionally by LRH-1, we have analyzed evolutionary conserved regions (ECRs) in HepG2 cells. One ECR was found to be responsive to the LRH-1. Through deletion studies, LRH-1 response element was identified and the binding of LRH-1 was demonstrated by EMSA and ChIP assays. When SREBP2, one of several transcription factors which had been shown to regulate NPC1L1 gene, was co-expressed with LRH-1, synergistic transcriptional activation resulted. In conclusion, we have identified LRH-1 response elements in NPC1L1 gene and propose that LRH-1 and SREBP may play important roles in regulating NPC1L1 gene.
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KEYWORD
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Cholesterol, LRH-1, NPC1L1, SERBP2, Transcription
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