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rdf:type |
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lifeskim:mentions |
umls-concept:C0025914,
umls-concept:C0026809,
umls-concept:C0034987,
umls-concept:C0038323,
umls-concept:C0086418,
umls-concept:C0086860,
umls-concept:C0443199,
umls-concept:C0851285,
umls-concept:C1167622,
umls-concept:C1334896,
umls-concept:C1335073
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pubmed:issue |
27
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pubmed:dateCreated |
2004-6-28
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pubmed:abstractText |
Small heterodimer partner (SHP; NR0B2) is an unusual orphan nuclear receptor that lacks a conventional DNA-binding domain and acts as a modulator of transcriptional activities of a number of nuclear receptors. Herein, we report that the human SHP promoter (hSHP) is activated by sterol regulatory element-binding protein-1 (SREBP-1), which regulates the expression of various genes involved in cholesterol and fatty acid synthesis. Overexpression of SREBP-1 activated the human but not mouse SHP promoter, although SREBP-2 had little effect on the SHP promoter in CV-1 cells. Serial deletion reporter assays revealed that SREBP-1-responsive region is located within the sequences from -243 to -120 bp in the hSHP promoter. DNase I footprinting, gel shift assays, and chromatin immunoprecipitation assays demonstrated that SREBP-1 binds directly to the hSHP promoter. Site-directed mutagenesis made it clear that the hSHP promoter activation by SREBP-1 is mostly mediated by the SRE1 (-186 to -195 bp) in the hSHP promoter, which is not conserved in the mouse SHP promoter. Moreover, adenovirus-mediated overexpression of SREBP-1c/ADD-1 induced SHP mRNA expression and repressed CYP7A1 expression in HepG2 cells. Finally, we found that a four-nucleotide deletion (-195CT-GAdel) in the hSHP promoter, which is reported to be associated with altered body weight and insulin secretion in human, coincides with the SRE1. This mutation strongly decreased both basal and SREBP-1 dependent activities of the hSHP promoter, because of the reduced binding of SREBP-1 to the mutated SRE1. Overall, our results demonstrate a differential regulation of human and mouse SHP promoters by SREBP-1. We propose a possible role of SREBP-1 in the species differential regulation of cholesterol and bile acid homeostasis via a novel mechanism of up-regulation of the hSHP gene expression.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyribonuclease I,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/SREBF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SREBF2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Srebf1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Srebf2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/nuclear receptor subfamily 0...
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
2
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
28122-31
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15123650-Adenoviridae,
pubmed-meshheading:15123650-Animals,
pubmed-meshheading:15123650-Base Sequence,
pubmed-meshheading:15123650-Blotting, Northern,
pubmed-meshheading:15123650-Body Weight,
pubmed-meshheading:15123650-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:15123650-Cell Line,
pubmed-meshheading:15123650-Cholesterol,
pubmed-meshheading:15123650-Chromatin,
pubmed-meshheading:15123650-DNA,
pubmed-meshheading:15123650-DNA-Binding Proteins,
pubmed-meshheading:15123650-Deoxyribonuclease I,
pubmed-meshheading:15123650-Fatty Acids,
pubmed-meshheading:15123650-Gene Deletion,
pubmed-meshheading:15123650-Gene Expression Regulation,
pubmed-meshheading:15123650-Humans,
pubmed-meshheading:15123650-Insulin,
pubmed-meshheading:15123650-Luciferases,
pubmed-meshheading:15123650-Mice,
pubmed-meshheading:15123650-Models, Genetic,
pubmed-meshheading:15123650-Molecular Sequence Data,
pubmed-meshheading:15123650-Mutagenesis, Site-Directed,
pubmed-meshheading:15123650-Precipitin Tests,
pubmed-meshheading:15123650-Promoter Regions, Genetic,
pubmed-meshheading:15123650-Protein Structure, Tertiary,
pubmed-meshheading:15123650-RNA, Messenger,
pubmed-meshheading:15123650-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:15123650-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15123650-Species Specificity,
pubmed-meshheading:15123650-Sterol Regulatory Element Binding Protein 1,
pubmed-meshheading:15123650-Sterol Regulatory Element Binding Protein 2,
pubmed-meshheading:15123650-Time Factors,
pubmed-meshheading:15123650-Transcription Factors,
pubmed-meshheading:15123650-Transcriptional Activation,
pubmed-meshheading:15123650-Transfection,
pubmed-meshheading:15123650-Up-Regulation
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pubmed:year |
2004
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pubmed:articleTitle |
Differential regulation of human and mouse orphan nuclear receptor small heterodimer partner promoter by sterol regulatory element binding protein-1.
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pubmed:affiliation |
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Kwangju 500-757, Republic of Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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