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Papers In Press, published online ahead of print September 28, 2001
Molecular Immunology, Curtin University of Technology, Perth, WA 6000
Corresponding Author: gretchen{at}cyllene.uwa.edu.au
Interleukin-5 (IL-5) is a T-cell cytokine involved in Type 2 diseases and is commonly described as being coordinately regulated with other Type 2 cytokines such as IL-4 and IL-13. Considering the unique control of eosinophilia by IL-5, such coordinate regulation would be surprising. In fact, the biological specificity of eosinophilia and its control by IL-5 suggests a unique and independent control of IL-5 regulation. In this report we show binding of GATA-3 to three sites in the human IL-5 promoter in the human T-cell line PER117. The previously identified -70 site and another site at position -152 are shown to positively regulate IL-5 transcription. More importantly, the site located at -400 acts as a powerful repressor of IL-5 transcription, with mutagenesis of this site allowing high level expression of IL-5 without activation of other factors normally required for IL-5 expression. While GATA-3 has been proposed to be involved in regulation of the IL-4/IL-5/IL-13 locus, we show here that it has another function controlling IL-5 transcription that supports the observed unique biological function of this cytokine.
J. Biol. Chem, 10.1074/jbc.M107836200
Submitted on August 15, 2001
Revised on September 11, 2001
Accepted on September 28, 2001
GATA-3 has dual regulatory functions in human IL-5 transcription
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