Transcriptional profiling of interferon regulatory factor 3 target genes: Direct involvement in the regulation of interferon-stimulated genes
Transcriptional profiling of interferon regulatory factor 3 target genes: Direct involvement in the regulation of interferon-stimulated genes
复制标题
DOI：
10.1128/jvi.76.11.5532-5539.2002
复制
发表时间：
2002-06-01
影响因子：
5.4
通讯作者：
Hiscott, J
中科院分区：
文献类型：
--
作者：
Grandvaux, N;Servant, MJ;Hiscott, J
泛素表达干扰素调节因子3 （IRF-3）在病毒感染后被直接激活，是立即早期α / β干扰素（IFN）基因和RANTES趋化因子基因的关键激活因子。在本研究中，将四环素诱导的表达IRF-3组成活性形式（irf - 35d）的表达系统与DNA微阵列分析相结合，以鉴定受IRF-3调控的靶基因。在tet诱导下表达irf - 35d后，监测8,556个基因mRNA表达谱的变化。在IRF-3上调的基因中，有几个已知的ifn刺激基因（ISGs）的转录本。随后的分析表明，IRF-3通过ISG56启动子的ifn刺激响应元件（ISREs）以不依赖ifn的方式直接诱导ISG56的表达。这些结果表明，IRF-3除了在功能性的即时早期ifn - β增强体的形成中发挥作用外，还能够区分isre含有的基因，这些基因参与抗病毒状态的建立，作为对病毒感染的直接反应。
Ubiquitously expressed interferon regulatory factor 3 (IRF-3) is directly activated after virus infection and functions as a key activator of the immediate-early alpha/beta interferon (IFN) genes, as well as the RANTES chemokine gene. In the present study, a tetracycline-inducible expression system expressing a constitutively active form of IRF-3 (IRF-3 5D) was combined with DNA microarray analysis to identify target genes regulated by IRF-3. Changes in mRNA expression profiles of 8,556 genes were monitored after Tet-inducible expression of IRF-3 5D. Among the genes upregulated by IRF-3 were transcripts for several known IFN-stimulated genes (ISGs). Subsequent analysis revealed that IRF-3 directly induced the expression of ISG56 in an IFN-independent manner through the IFN-stimulated responsive elements (ISREs) of the ISG56 promoter. These results demonstrate that, in addition to its role in the formation of a functional immediate-early IFN-beta enhanceosome, IRF-3 is able to discriminate among ISRE-containing genes involved in the establishment of the antiviral state as a direct response to virus infection.