Abstract
The development of Th subset is accompanied by subset-specific chromatin remodeling of cytokine gene loci. In this study, we show that the C-terminal, but not the N-terminal zinc finger (N-finger) of GATA-3 mediates the association with the IL-4/IL-13 intergenic DNase I hypersensitive site and the induction of an extended DNase I hypersensitivity on the IL-4/IL-13 locus. Consistently, deletion of the transactivation domains or the C-finger, but not the N-finger, abrogated the induction of IL-4 and IL-13 as well as the down-regulation of IFN-gamma. In contrast, the N-finger of GATA-3 was indispensable for the binding to the IL-5 promoter and the induction of IL-5. The selective use of the N-finger may underlie the differential roles of GATA-3 in the induction of IL-4, IL-13, and IL-5.
MeSH terms
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Animals
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Chromatin / genetics
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Chromatin / metabolism*
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DNA / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology*
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GATA3 Transcription Factor
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Interleukin-13 / biosynthesis
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Interleukin-4 / biosynthesis
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Interleukin-5 / biosynthesis
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Mice
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Mutagenesis, Site-Directed
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Protein Binding / genetics
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Protein Binding / immunology
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Protein Structure, Tertiary / genetics
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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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Trans-Activators / genetics
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Trans-Activators / metabolism
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Trans-Activators / physiology*
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Transcriptional Activation / immunology*
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Zinc Fingers* / genetics
Substances
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Chromatin
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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-13
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Interleukin-5
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Trans-Activators
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Interleukin-4
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DNA