Transcriptional regulation of Niemann-Pick C1-like 1 gene by liver receptor homolog-1.
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.
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 24252, Korea.
Eui Sup
ES
Lee
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 24252, Korea.
Hyun Jung
HJ
Seo
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 24252, Korea.
Su Sun
SS
Back
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 24252, Korea.
Seung Ho
SH
Han
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 24252, Korea.
Yeon Ji
YJ
Jeong
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 24252, Korea.
Jin Wook
JW
Lee
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 24252, Korea.
Soo Young
SY
Choi
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 24252, Korea.
Kyuhyung
K
Han
D002784:Cholesterol / Q000378:metabolism; D017124:Conserved Sequence; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism
D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; C082631:NR5A2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; C497390:SREBF2 protein, human; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol