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

AbstractThe 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