rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0017337,
umls-concept:C0021641,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0038323,
umls-concept:C0127400,
umls-concept:C0185117,
umls-concept:C0205217,
umls-concept:C0220905,
umls-concept:C0871261,
umls-concept:C1335858,
umls-concept:C1516240,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911684,
umls-concept:C2911692
|
pubmed:issue |
24
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pubmed:dateCreated |
2007-6-11
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pubmed:abstractText |
The induction of genes involved in lipid biosynthesis by insulin is mediated in part by the sterol regulatory element-binding protein-1c (SREBP-1c). SREBP-1c is directly regulated by insulin by transcriptional and post-transcriptional mechanisms. Previously, we have demonstrated that the insulin-responsive cis-acting unit of the rat SREBP-1c promoter is composed of several elements that include a sterol regulatory element, two liver X receptor elements, and a number of conserved GC boxes. Here we systematically dissected the role of these GC boxes and report that five bona fide Sp1-binding elements of the SREBP-1c promoter determine its basal and insulin-induced activation. Luciferase expression driven by the rat SREBP-1c promoter was accelerated by ectopic expression of Sp1, and insulin further enhanced the transactivation potential of Sp1. Introduction of a small interfering RNA against Sp1 reduced both basal and insulin-induced activation of the SREBP-1c promoter. We also found that Sp1 interacted with both SREBP-1c and LXRalpha proteins and that insulin promoted these interactions. Chromatin immunoprecipitation studies revealed that insulin facilitated the recruitment of the steroid receptor coactivator-1 to the SREBP-1c promoter. These studies identify a novel mechanism by which maximal activation of the rat SREBP-1c gene expression by insulin is mediated by Sp1 and its enhanced ability to interact with other transcriptional regulatory proteins.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CREB-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/NCOA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Coactivator 1,
http://linkedlifedata.com/resource/pubmed/chemical/Orphan Nuclear Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol Regulatory Element Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/liver X receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
17517-29
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17449871-Animals,
pubmed-meshheading:17449871-CREB-Binding Protein,
pubmed-meshheading:17449871-Cell Line,
pubmed-meshheading:17449871-DNA-Binding Proteins,
pubmed-meshheading:17449871-Gene Expression Regulation,
pubmed-meshheading:17449871-Genes, Reporter,
pubmed-meshheading:17449871-Histone Acetyltransferases,
pubmed-meshheading:17449871-Humans,
pubmed-meshheading:17449871-Insulin,
pubmed-meshheading:17449871-Male,
pubmed-meshheading:17449871-Nuclear Receptor Coactivator 1,
pubmed-meshheading:17449871-Orphan Nuclear Receptors,
pubmed-meshheading:17449871-Promoter Regions, Genetic,
pubmed-meshheading:17449871-RNA Interference,
pubmed-meshheading:17449871-Rats,
pubmed-meshheading:17449871-Rats, Sprague-Dawley,
pubmed-meshheading:17449871-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:17449871-Sp1 Transcription Factor,
pubmed-meshheading:17449871-Sterol Regulatory Element Binding Protein 1,
pubmed-meshheading:17449871-Transcription Factors,
pubmed-meshheading:17449871-Transcriptional Activation
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pubmed:year |
2007
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pubmed:articleTitle |
Expression of the rat sterol regulatory element-binding protein-1c gene in response to insulin is mediated by increased transactivating capacity of specificity protein 1 (Sp1).
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pubmed:affiliation |
Medical and Research Service, Department of Veterans Affairs Medical Center, Memphis, Tennessee 38104, USA. xdeng@utmem.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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