Abstract
Th1 and Th2 cells differentiate from naive precursors to effector cells that produce either IFN-gamma or IL-4, respectively. To identify transcriptional paths leading to activation and silencing of the IFN-gamma gene, we analyzed transgenic mice that express a reporter gene under the control of the 5' IFN-gamma promoter. We found that as the length of the promoter is increased, -110 to -225 to -565 bp, the activity of the promoter undergoes a transition from Th1 nonselective to Th1 selective. This is due, at least in part, to a T box expressed in T cells-responsive unit within the -565 to -410 region of the IFN-gamma promoter. The -225 promoter is silent when compared with the -110 promoter and silencing correlates with Yin Yang 1 binding to the promoter. The p38 mitogen-activated protein kinase signaling pathway, which also regulates IFN-gamma gene transcription, regulates the -70- to -44-bp promoter element. Together, the results demonstrate that a minimal IFN-gamma promoter contains a T box expressed in T cells responsive unit and is sufficient to confer Th1 selective expression upon a reporter.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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5' Untranslated Regions / immunology
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Animals
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Base Sequence
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Cells, Cultured
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology
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Erythroid-Specific DNA-Binding Factors
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Gene Expression Regulation / immunology
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Humans
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Interferon-gamma / genetics*
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Interferon-gamma / metabolism
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Jurkat Cells
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MAP Kinase Signaling System / immunology
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Mice
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Mice, Transgenic
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Mitogen-Activated Protein Kinases / physiology
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Molecular Sequence Data
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Promoter Regions, Genetic / immunology*
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Protein Binding / immunology
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Response Elements / immunology
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T-Box Domain Proteins
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T-bet Transcription Factor
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Th1 Cells / cytology
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Th1 Cells / enzymology
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Th1 Cells / immunology*
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Th1 Cells / metabolism*
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Trans-Activators / genetics
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Trans-Activators / isolation & purification
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Trans-Activators / physiology
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Transcription Factors / genetics
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Transcription Factors / isolation & purification
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Transcription Factors / metabolism
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Transcription Factors / physiology
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YY1 Transcription Factor
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p38 Mitogen-Activated Protein Kinases
Substances
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5' Untranslated Regions
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DNA-Binding Proteins
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Erythroid-Specific DNA-Binding Factors
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T-Box Domain Proteins
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T-bet Transcription Factor
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Trans-Activators
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Transcription Factors
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YY1 Transcription Factor
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Interferon-gamma
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases