GATA-3 suppresses IFN-γ promoter activity independently of binding to cis-regulatory elements
GATA-3 suppresses IFN-γ promoter activity independently of binding to cis-regulatory elements
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DOI：
10.1016/j.febslet.2004.06.026
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发表时间：
2004-07-16
期刊：
影响因子：
3.5
通讯作者：
Miyatake, S
中科院分区：
文献类型：
--
作者：
Kaminuma, O;Kitamura, F;Miyatake, S
研究了加塔-3抑制IFN-γ基因表达的调节机制。使用RNA干扰技术减少加塔-3增强，而过表达加塔-3抑制IFN-γ mRNA表达。IL-4表达受加塔-3的间接影响。通过抑制IFN-γ的启动子/增强子活性实现了加塔-3介导的IFN-γ下调。位于顺式调节元件中的两个加塔元件并不有助于IFN-γ启动子活性的抑制，即使它们表现为加塔-3的结合位点。除去-257至-172的区域后，加塔-3对IFN-γ启动子的作用丧失。在与该区域相互作用的转录因子中，增强IFN-γ启动子活性的Stat 4在基因转录水平被加塔-3下调。尽管加塔-3具有与顺式调节元件相互作用的能力，但其通过下调Stat 4抑制IFN-γ基因转录。(C)2004年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
The regulatory mechanism by which GATA-3 suppresses IFN-gamma gene expression was investigated. A reduction of GATA-3 using RNA interference technology enhanced, whereas overexpression of GATA-3 suppressed IFN-gamma mRNA expression. IL-4 expression was reciprocally affected by GATA-3. GATA-3-mediated down-regulation of IFN-gamma 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-gamma promoter activity, even though they, behaved as binding sites for GATA-3. The effect of GATA-3 on IFN-gamma 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-gamma 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-gamma gene transcription via down-regulation of Stat4. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.