Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2007-6-11
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17517-29
pubmed:dateRevised
2011-11-17
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
pubmed:year
2007
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).
pubmed:affiliation
Medical and Research Service, Department of Veterans Affairs Medical Center, Memphis, Tennessee 38104, USA. xdeng@utmem.edu
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