Characterization of P5, a novel NFAT/AP-1 site in the human IL-4 promoter.
Interleukin 4 (IL-4) gene expression is controlled at the level of transcription by the complex interactions of multiple factors that bind to a proximal promoter region. Nuclear factor of activated T cells (NFAT) can bind up to five purine-rich sequences in the IL-4 promoter termed the P elements (P0-P4). In this paper, we characterize a novel P element in the upstream region of the human IL-4 promoter that we term P5. P5 shares a core NFAT motif ((-353)GGAAA(-357)) and additional sequence similarity with the other P elements and supported strong interactions between the NFATp DNA-binding domain (DBD) and the AP-1 proteins cFos and cJun in DNA-binding assays. Inducibility of the IL-4 promoter was significantly impaired in a reporter construct in which the P5 element was mutated in the context of the full-length promoter. We conclude that P5 represents a novel IL-4 promoter P element that contributes to IL-4 promoter inducibility.
Burke
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Division of Pulmonary and Critical Care Medicine, The Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224, USA.
Casolaro
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Georas
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D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D015847:Interleukin-4