Abstract
Interleukin-3 (IL-3) is a cytokine that is expressed primarily in activated T cells. Here we identified an inducible T cell-specific enhancer 14 kb upstream of the IL-3 gene that responded to activation of T cell receptor signaling pathways. The IL-3 enhancer spanned an inducible cyclosporin A-sensitive DNase I-hypersensitive site found only in T cells. Four NFAT-like elements exist within the enhancer. The two most active NFAT-like elements were located at the center of the DNase I-hypersensitive site. One of these NFAT-like elements encompassed overlapping Oct- and NFATp/c-binding sites, which functioned in a highly synergistic manner. We suggest that the T cell-specific expression of the IL-3 gene is partly controlled through the enhancer by cooperation between Oct and NFAT family proteins.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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Cyclosporine / toxicity
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DNA-Binding Proteins / pharmacology*
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Deoxyribonuclease I / pharmacology*
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Drug Synergism
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Enhancer Elements, Genetic / drug effects
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Enhancer Elements, Genetic / immunology*
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Gene Expression Regulation / immunology*
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HeLa Cells
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Homeodomain Proteins / pharmacology*
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Host Cell Factor C1
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Humans
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Interleukin-3 / genetics*
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Jurkat Cells
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Molecular Sequence Data
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NFATC Transcription Factors
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Nuclear Proteins*
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Octamer Transcription Factor-1
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Octamer Transcription Factor-2
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T-Lymphocytes / metabolism*
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Transcription Factors / pharmacology*
Substances
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DNA-Binding Proteins
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HCFC1 protein, human
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Homeodomain Proteins
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Host Cell Factor C1
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Interleukin-3
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NFATC Transcription Factors
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Nuclear Proteins
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Octamer Transcription Factor-1
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Octamer Transcription Factor-2
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POU2F1 protein, human
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POU2F2 protein, human
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Transcription Factors
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Cyclosporine
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Deoxyribonuclease I