GATA-3 has dual regulatory functions in human interleukin-5 transcription.
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 the 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 a high level expression of IL-5 without the activation of other factors normally required for IL-5 expression. Whereas GATA-3 has been proposed to be involved in the regulation of the IL-4/IL-5/IL-13 locus, we show here that it has another function in controlling IL-5 transcription that supports the observed unique biological function of this cytokine.
Schwenger
G T
GT
Department of Molecular Immunology, Curtin University of Technology, and the Western Australian Institute of Medical Research Level 5, Medical Research Foundation Building, Rear 50 Murray Street, Perth 6000, Western Australia. gretchen@cyllene.uwa.edu.au
Fournier
R
R
Kok
C C
CC
Mordvinov
V A
VA
Yeoman
D
D
Sanderson
C J
CJ
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D015848:Interleukin-5; D015534:Trans-Activators; D004247:DNA