GATA-3抑制干扰素-γ启动子活性，且不依赖于与顺式调控元件的结合。

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

作者信息

Kaminuma Osamu, Kitamura Fujiko, Kitamura Noriko, Miyagishi Makoto, Taira Kazunari, Yamamoto Koh, Miura Osamu, Miyatake Shoichiro

机构信息

Department of Immunology, The Tokyo Metropolitan Institute of Medical Science, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.

出版信息

FEBS Lett. 2004 Jul 16;570(1-3):63-8. doi: 10.1016/j.febslet.2004.06.026.

DOI:10.1016/j.febslet.2004.06.026

PMID:15251440

Abstract

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.

摘要

研究了GATA-3抑制IFN-γ基因表达的调控机制。使用RNA干扰技术降低GATA-3可增强IFN-γ mRNA表达，而GATA-3的过表达则抑制其表达。IL-4的表达受到GATA-3的反向影响。GATA-3介导的IFN-γ下调是通过抑制其启动子/增强子活性实现的。位于顺式调控元件中的两个GATA元件，尽管它们作为GATA-3的结合位点，但对IFN-γ启动子活性的抑制没有作用。去除包含-257至-172的区域后，GATA-3对IFN-γ启动子的作用消失。在可能与该区域相互作用的几种转录因子中，增强IFN-γ启动子活性的Stat4在基因转录水平上被GATA-3下调。尽管GATA-3有能力与顺式调控元件相互作用，但它通过下调Stat4来抑制IFN-γ基因转录。