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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11
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pubmed:dateCreated |
1998-12-21
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pubmed:abstractText |
Before they can deliver their effector functions, CD4+ Th cells must differentiate into Th1 or Th2 subsets. We have prepared reporter transgenic mice that express the luciferase gene under the control of proximal (prox.IFN-gamma) and distal (dist.IFN-gamma) regulatory elements from the IFN-gamma promoter to permit investigation of mechanisms that regulate IFN-gamma gene transcription during Th cell differentiation. Precursor Th cells (pTh) contain high levels of cAMP response element binding protein-activation transcription factor-1 (CREB-ATF1) proteins that bind these promoter elements from the IFN-gamma gene, and these cells fail to express promoter activity. Restimulated effector Th (eTh) cells have reduced levels of CREB-ATF1 proteins, their nuclear extracts exhibit reduced CREB-ATF1 binding and greater Jun and Jun-ATF2 binding to dist.IFN-gamma), and eTh cells express promoter activity. CREB directly competes with effector T cell nuclear proteins for dist.IFN-gamma binding, and overexpression of CREB inhibits both prox.IFN-gamma- and dist.IFN-gamma-directed transcription in Jurkat T cells. IL-12-stimulated Thl differentiation increases dist.IFN-gamma activity in restimulated eTh1 cells; eTh1 nuclear extracts form increased levels of Jun-ATF2-dist.IFN-gamma complexes. Taken together, these data suggest that both de-repression and trans-activation contribute to the induction of IFN-gamma gene transcription during Th1 differentiation.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
161
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6105-12
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9834094-Animals,
pubmed-meshheading:9834094-Binding, Competitive,
pubmed-meshheading:9834094-Cell Differentiation,
pubmed-meshheading:9834094-Cells, Cultured,
pubmed-meshheading:9834094-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:9834094-Down-Regulation,
pubmed-meshheading:9834094-Interferon-gamma,
pubmed-meshheading:9834094-Interleukin-12,
pubmed-meshheading:9834094-Mice,
pubmed-meshheading:9834094-Mice, Inbred C57BL,
pubmed-meshheading:9834094-Mice, Inbred CBA,
pubmed-meshheading:9834094-Mice, Transgenic,
pubmed-meshheading:9834094-Nuclear Proteins,
pubmed-meshheading:9834094-Promoter Regions, Genetic,
pubmed-meshheading:9834094-Protein Binding,
pubmed-meshheading:9834094-Regulatory Sequences, Nucleic Acid,
pubmed-meshheading:9834094-T-Lymphocytes, Helper-Inducer,
pubmed-meshheading:9834094-Th1 Cells,
pubmed-meshheading:9834094-Transcription Factor AP-1
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pubmed:year |
1998
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pubmed:articleTitle |
Regulation of the activity of IFN-gamma promoter elements during Th cell differentiation.
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pubmed:affiliation |
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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