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

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Abstract
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.