Source:http://linkedlifedata.com/resource/pubmed/id/16318585
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
2005-12-1
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pubmed:abstractText |
Regulation of gene transcription by the cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) involves complex interactions between NF-kappaB and Stat families of transcription factors. The purpose of this study was to identify the spatial promoter requirements that govern cytokine synergy for gene transcription regulated by NF-kappaB and Stat factors. Using a set of transcription reporter-luciferase constructs, we show that the relative orientation of juxtaposed NF-kappaB-Stat (SIE) cis-elements determines the ability of TNF-alpha and IFN- gamma to induce gene transcription. Further, NF-kappaB and Stat1 proteins directly regulate transcription by interacting cooperatively on NF-kappaB-SIE DNA binding in response to TNF-alpha plus IFN-gamma. Coimmunoprecipitation provides evidence for a direct NF-kappaB/Stat1 protein-protein interaction. In contrast, IFN-gamma inhibits TNF-alpha-induced transcription of an NF-kappaB reporter gene in a Stat1-dependent mechanism in 2fTGH fibroblasts. Similarly, Stat1 is inhibitory to NF-kappaB overexpression-induced transcription. IFN-gamma and Stat1-dependent inhibition of NF-kappaB transcription occurs independent of TNF-alpha-induced NF-kappaB DNA binding. Interestingly, IFN-gamma pretreatment of 2fTGH fibroblasts potentiates TNF-alpha induction of Stat1 DNA binding. Further, ChIP analysis was applied to detect cytokine-induced in vivo binding and transcriptional regulation of the human inducible nitric oxide synthase (iNOS) gene by NF-kappaB and Stat1. These data demonstrate complex transcriptional regulatory mechanisms elicited by TNF-alpha and IFN-gamma and have potentially important implications for other genes differentially controlled by cytokines.
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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/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1079-9907
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
707-19
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:16318585-Cell Line, Tumor,
pubmed-meshheading:16318585-Chromatin,
pubmed-meshheading:16318585-Chromatin Immunoprecipitation,
pubmed-meshheading:16318585-Cytokines,
pubmed-meshheading:16318585-DNA,
pubmed-meshheading:16318585-Fibroblasts,
pubmed-meshheading:16318585-Gene Expression Regulation,
pubmed-meshheading:16318585-Genes, Reporter,
pubmed-meshheading:16318585-Humans,
pubmed-meshheading:16318585-Immunoprecipitation,
pubmed-meshheading:16318585-Inflammation,
pubmed-meshheading:16318585-Interferon-gamma,
pubmed-meshheading:16318585-Luciferases,
pubmed-meshheading:16318585-NF-kappa B,
pubmed-meshheading:16318585-Oligonucleotides,
pubmed-meshheading:16318585-Plasmids,
pubmed-meshheading:16318585-Protein Binding,
pubmed-meshheading:16318585-STAT1 Transcription Factor,
pubmed-meshheading:16318585-Trans-Activators,
pubmed-meshheading:16318585-Transcription, Genetic,
pubmed-meshheading:16318585-Transfection,
pubmed-meshheading:16318585-Tumor Necrosis Factor-alpha
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pubmed:year |
2005
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pubmed:articleTitle |
Differential effects of TNF-alpha and IFN-gamma on gene transcription mediated by NF-kappaB-Stat1 interactions.
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pubmed:affiliation |
Department of Surgery, University of Pittsburgh School of Medicine, PA 15261, USA.
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pubmed:publicationType |
Journal Article
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