Abstract
Sox4 is a transcription factor that regulates various developmental processes. Here we show that Sox4 was induced by TGF-β and negatively regulated the transcription factor GATA-3, the master regulator of function of T helper type 2 (T(H)2) cells, by two distinct mechanisms. First, Sox4 bound directly to GATA-3, preventing its binding to GATA-3 consensus DNA sequences. Second, Sox4 bound to the promoter region of the gene encoding interleukin 5 (IL-5), a T(H)2 cytokine, and prevented binding of GATA-3 to this promoter. T(H)2 cell-driven airway inflammation was modulated by alterations in Sox4 expression. Thus, Sox4 acted as a downstream target of TGF-β to inhibit GATA-3 function, T(H)2 differentiation and T(H)2 cell-mediated inflammation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation
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Cells, Cultured
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DNA-Binding Proteins / antagonists & inhibitors
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GATA3 Transcription Factor / biosynthesis
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GATA3 Transcription Factor / metabolism*
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Interferon-gamma / biosynthesis
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Interleukin-5 / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Pneumonia / immunology
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Promoter Regions, Genetic
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RNA Interference
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RNA, Small Interfering
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SOXC Transcription Factors / genetics*
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SOXC Transcription Factors / metabolism*
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Signal Transduction
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Th2 Cells / cytology*
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Th2 Cells / immunology
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Th2 Cells / metabolism
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism*
Substances
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DNA-Binding Proteins
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GATA3 Transcription Factor
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Gata3 protein, mouse
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Interleukin-5
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RNA, Small Interfering
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SOXC Transcription Factors
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Sox4 protein, mouse
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Transforming Growth Factor beta
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Interferon-gamma