Abstract:
: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.
journal_name
BMB Repjournal_title
BMB reportsauthors
Lee ES,Seo HJ,Back SS,Han SH,Jeong YJ,Lee JW,Choi SY,Han Kdoi
10.5483/bmbrep.2015.48.9.253subject
Has Abstractpub_date
2015-09-01 00:00:00pages
513-8issue
9eissn
1976-6696issn
1976-670Xpii
3047journal_volume
48pub_type
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