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http://dx.doi.org/10.5483/BMBRep.2015.48.9.253

Transcriptional regulation of Niemann-Pick C1-like 1 gene by liver receptor homolog-1  

Lee, Eui Sup (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
Seo, Hyun Jung (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
BacK, Su Sun (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
Han, Seung Ho (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
Jeong, Yeon Ji (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
Lee, Jin Wook (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
Choi, Soo Young (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
Han, Kyuhyung (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
Publication Information
BMB Reports / v.48, no.9, 2015 , pp. 513-518 More about this Journal
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. [BMB Reports 2015; 48(9): 513-518]
Keywords
Cholesterol; LRH-1; NPC1L1; SERBP2; Transcription;
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Times Cited By KSCI : 1  (Citation Analysis)
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1 Fayard E, Schoonjans K, Annicotte JS and Auwerx J (2003) Liver receptor homolog 1 controls the expression of carboxyl ester lipase. J Biol Chem 278, 35725-35731   DOI
2 Out C, Hageman J, Bloks VW et al (2011) Liver receptor homolog-1 is critical for adequate up-regulation of Cyp7a1 gene transcription and bile salt synthesis during bile salt sequestration. Hepatology 53, 2075-2085   DOI
3 Song X, Kaimal R, Yan B and Deng R. (2008) Liver receptor homolog 1 transcriptionally regulates human bile salt export pump expression. J Lipid Res 49, 973-984   DOI
4 Matsukuma KE, Wang L, Bennett MK and Osborne TF. (2007) A key role for orphan nuclear receptor liver receptor homologue-1 in activation of fatty acid synthase promoter by liver X receptor. J Biol Chem 282, 20164-71   DOI
5 Pramfalk C, Jiang ZY, Cai, Q et al (2010) HNF1alpha and SREBP2 are important regulators of NPC1L1 in human liver. J Lipid Res 51, 1354-1362   DOI
6 Iwayanagi Y, Takada T and Suzuki H (2008) HNF4alpha is a crucial modulator of the cholesterol-dependent regulation of NPC1L1. Pharm Res 25, 1134-41   DOI
7 Iwayanagi Y, Takada T, Tomura F et al (2011) Human NPC1L1 expression is positively regulated by PPAR. Pharm Res 28, 405-412   DOI
8 Alrefai WA, Annaba F, Sarwar Z et al (2007) Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2. Am J Physiol Gastrointest Liver Physiol 292, G369-376   DOI
9 Davies JP, Levy B and Ioannou YA (2000) Evidence for a Niemann-Pick C (NPC) gene family: identification and characterization of NPC1L1, Genomics 65, 137-145   DOI
10 Back SS, Kim J, Choi D, Lee ES, Choi SY and Han K (2013) Cooperative transcriptional activation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 genes by nuclear receptors including Liver-X-Receptor. BMB Rep 46, 322-327   DOI
11 Temel RE, Tang W, Ma Y et al (2007) Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe. J Clin Invest 117, 1968-1978   DOI
12 The Myocardial Infarction Genetics Consortium Investigators (2014) Inactivating Mutations in NPC1L1 and Protec- tion from Coronary Heart Disease. N Engl J Med 371, 2072-2082   DOI
13 Schoonjans K, Annicotte JS, Huby T et al (2002) Liver receptor homolog 1 controls the expression of the scavenger receptor class B type I. EMBO Rep 3, 1181-1187   DOI
14 Garcia-Calvo M, Lisnock J, Bull HG et al (2005) The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A 102, 8132-8137   DOI
15 Stein S, Oosterveer MH, Mataki C et al (2014) SUMOylationDependent LRH-1/PROX1 Interaction Promotes Atherosclerosis by Decreasing Hepatic Reverse Cholesterol Transport. Cell Metab 20, 603-613   DOI
16 Fayard E, Auwerx J and Schoonjans K (2004) LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis. Trends Cell Biol 14, 250-260   DOI
17 Freeman LA, Kennedy A, Wu J et al (2004) The orphan nuclear receptor LRH-1 activates the ABCG5/ABCG8 intergenic promoter. J Lipid Res 45, 1197-1206   DOI
18 Delerive P, Galardi CM, Bisi JE, Nicodeme E and Goodwin B (2004) Identification of liver receptor homolog-1 as a novel regulator of apolipoprotein AI gene transcription. Mol Endocrinol 18, 2378-2387   DOI
19 Luo Y, Liang CP and Tall AR (2001) The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor. J Biol Chem 276, 24767-24773   DOI
20 Altmann SW, Davis HR Jr, Zhu LJ et al (2004) Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 303, 1201-1204   DOI