rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2003-3-31
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pubmed:abstractText |
HMGI-Y is an architectural transcription factor that regulates gene expression in vivo by controlling the formation of stereospecific multiprotein complexes on the AT-rich regions of certain gene promoters. Recently, we demonstrated that HMGI-Y is required for proper transcription of the insulin receptor (IR) gene. Here we provide evidence that transcriptional activation of the human IR promoter requires the assembly of a transcriptionally active multiprotein-DNA complex which includes, in addition to HMGI-Y, the ubiquitously expressed transcription factor Sp1 and the CCAAT-enhancer binding protein beta (C/EBP beta). Functional integrity of this nucleoprotein complex is required for full transactivation of the IR gene by Sp1 and C/EBP beta in cells readily expressing IRs. We show that HMGI-Y physically interacts with Sp1 and C/EBP beta and facilitates the binding of both factors to the IR promoter in vitro. Furthermore, HMGI-Y is needed for transcriptional synergism between these factors in vivo. Repression of HMGI-Y function adversely affects both Sp1- and C/EBP beta-induced transactivation of the IR promoter. Together, these findings demonstrate that HMGI-Y plays significant molecular roles in the transcriptional activities of these factors in the context of the IR gene and provide concordant support for the hypothesis that, in affected individuals, a putative defect in these nuclear proteins may cause decreased IR expression with subsequent impairment of insulin signaling and action.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12665574-10194465,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12665574-10199397,
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0270-7306
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2720-32
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pubmed:dateRevised |
2010-3-2
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pubmed:meshHeading |
pubmed-meshheading:12665574-3T3 Cells,
pubmed-meshheading:12665574-Animals,
pubmed-meshheading:12665574-Base Sequence,
pubmed-meshheading:12665574-Binding Sites,
pubmed-meshheading:12665574-CCAAT-Enhancer-Binding Protein-beta,
pubmed-meshheading:12665574-Cell Line,
pubmed-meshheading:12665574-Cell Transformation, Viral,
pubmed-meshheading:12665574-DNA,
pubmed-meshheading:12665574-Diabetes Mellitus,
pubmed-meshheading:12665574-HMGA1a Protein,
pubmed-meshheading:12665574-Herpesvirus 4, Human,
pubmed-meshheading:12665574-Humans,
pubmed-meshheading:12665574-Mice,
pubmed-meshheading:12665574-Models, Biological,
pubmed-meshheading:12665574-Nucleoproteins,
pubmed-meshheading:12665574-Promoter Regions, Genetic,
pubmed-meshheading:12665574-Receptor, Insulin,
pubmed-meshheading:12665574-Recombinant Proteins,
pubmed-meshheading:12665574-Signal Transduction,
pubmed-meshheading:12665574-Sp1 Transcription Factor,
pubmed-meshheading:12665574-Transcription, Genetic
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pubmed:year |
2003
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pubmed:articleTitle |
A nucleoprotein complex containing Sp1, C/EBP beta, and HMGI-Y controls human insulin receptor gene transcription.
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pubmed:affiliation |
Dipartimento di Medicina Sperimentale e Clinica G. Salvatore, Università degli Studi di Catanzaro Magna Graecia, 88100 Catanzaro, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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