GATA-3 suppresses IFN-γ promoter activity independently of binding to cis-regulatory elements

The regulatory mechanism by which GATA-3 suppresses IFN-γ gene expression was investigated. A reduction of GATA-3 using RNA interference technology enhanced, whereas overexpression of GATA-3 suppressed IFN-γ mRNA expression. IL-4 expression was reciprocally affected by GATA-3. GATA-3-mediated down-r...

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Bibliographic Details
Published in:FEBS letters 2004-07, Vol.570 (1), p.63-68
Main Authors: Kaminuma, Osamu, Kitamura, Fujiko, Kitamura, Noriko, Miyagishi, Makoto, Taira, Kazunari, Yamamoto, Koh, Miura, Osamu, Miyatake, Shoichiro
Format: Article
Language:English
Subjects:
Base Sequence
Binding Sites
Cell Nucleus - metabolism
DNA, Complementary - metabolism
DNA-Binding Proteins - metabolism
DNA-Binding Proteins - physiology
Down-Regulation
EMSA, electrophoresis mobility shift assay
Enhancer Elements, Genetic
Flow Cytometry
GATA-3
GATA3 Transcription Factor
Gene Expression Regulation
Genes, Reporter
Genetic Vectors
Green Fluorescent Proteins
Humans
IFN-γ
Immunoblotting
Interferon-gamma - genetics
Interleukin-4 - metabolism
Jurkat Cells
Luminescent Proteins - metabolism
MFI, mean fluorescence intensity
Models, Genetic
Molecular Sequence Data
Plasmids - metabolism
PMA, phorbol 12-myristate 13-acetate
Promoter Regions, Genetic
Protein Binding
RNA Interference
RNA, Messenger - metabolism
shRNA, short hairpin form siRNA
siRNA, small double stranded interfering RNA
Stat4
STAT4 Transcription Factor
Th1 Cells - metabolism
Th1/Th2
Th2 Cells - metabolism
Time Factors
Trans-Activators - metabolism
Trans-Activators - physiology
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Summary:The regulatory mechanism by which GATA-3 suppresses IFN-γ gene expression was investigated. A reduction of GATA-3 using RNA interference technology enhanced, whereas overexpression of GATA-3 suppressed IFN-γ mRNA expression. IL-4 expression was reciprocally affected by GATA-3. GATA-3-mediated down-regulation of IFN-γ was achieved through the inhibition of its promoter/enhancer activity. Two GATA elements located in the cis-regulatory elements did not contribute to the suppression of IFN-γ promoter activity, even though they behaved as binding sites for GATA-3. The effect of GATA-3 on IFN-γ promoter was lost upon removal of the region encompassing −257 to −172. Among several transcription factors putatively interacting with this region, Stat4, which enhanced IFN-γ promoter activity, was down-regulated by GATA-3 at gene transcription level. Although GATA-3 has the capacity to interact with the cis-regulatory elements, it suppresses IFN-γ gene transcription via down-regulation of Stat4.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2004.06.026