Mechanism for transcriptional synergy between interferon regulatory factor (IRF)-3 and IRF-7 in activation of the interferon-beta gene promoter.

Hongmei Yang, Gang Ma, Charles H Lin, Melissa Orr, Marc G Wathelet
{"title":"Mechanism for transcriptional synergy between interferon regulatory factor (IRF)-3 and IRF-7 in activation of the interferon-beta gene promoter.","authors":"Hongmei Yang,&nbsp;Gang Ma,&nbsp;Charles H Lin,&nbsp;Melissa Orr,&nbsp;Marc G Wathelet","doi":"10.1111/j.1432-1033.2004.04310.x","DOIUrl":null,"url":null,"abstract":"<p><p>The interferon-beta promoter has been studied extensively as a model system for combinatorial transcriptional regulation. In virus-infected cells the transcription factors ATF-2, c-Jun, interferon regulatory factor (IRF)-3, IRF-7 and NF-kappaB, and the coactivators p300/CBP play critical roles in the activation of this and other promoters. It remains unclear, however, why most other combinations of AP-1, IRF and Rel proteins fail to activate the interferon-beta gene. Here we have explored how different IRFs may cooperate with other factors to activate transcription. First we showed in undifferentiated embryonic carcinoma cells that ectopic expression of either IRF-3 or IRF-7, but not IRF-1, was sufficient to allow virus-dependent activation of the interferon-beta promoter. Moreover, the activity of IRF-3 and IRF-7 was strongly affected by promoter context, with IRF-7 preferentially being recruited to the natural interferon-beta promoter. We fully reconstituted activation of this promoter in insect cells. Maximal synergy required IRF-3 and IRF-7 but not IRF-1, and was strongly dependent on the presence of p300/CBP, even when these coactivators only modestly affected the activity of each factor by itself. These results suggest that specificity in activation of the interferon-beta gene depends on a unique promoter context and on the role played by coactivators as architectural factors.</p>","PeriodicalId":11817,"journal":{"name":"European journal of biochemistry","volume":"271 18","pages":"3693-703"},"PeriodicalIF":0.0000,"publicationDate":"2004-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1432-1033.2004.04310.x","citationCount":"54","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of biochemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1111/j.1432-1033.2004.04310.x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 54

Abstract

The interferon-beta promoter has been studied extensively as a model system for combinatorial transcriptional regulation. In virus-infected cells the transcription factors ATF-2, c-Jun, interferon regulatory factor (IRF)-3, IRF-7 and NF-kappaB, and the coactivators p300/CBP play critical roles in the activation of this and other promoters. It remains unclear, however, why most other combinations of AP-1, IRF and Rel proteins fail to activate the interferon-beta gene. Here we have explored how different IRFs may cooperate with other factors to activate transcription. First we showed in undifferentiated embryonic carcinoma cells that ectopic expression of either IRF-3 or IRF-7, but not IRF-1, was sufficient to allow virus-dependent activation of the interferon-beta promoter. Moreover, the activity of IRF-3 and IRF-7 was strongly affected by promoter context, with IRF-7 preferentially being recruited to the natural interferon-beta promoter. We fully reconstituted activation of this promoter in insect cells. Maximal synergy required IRF-3 and IRF-7 but not IRF-1, and was strongly dependent on the presence of p300/CBP, even when these coactivators only modestly affected the activity of each factor by itself. These results suggest that specificity in activation of the interferon-beta gene depends on a unique promoter context and on the role played by coactivators as architectural factors.

干扰素调节因子(IRF)-3和IRF-7在干扰素- β基因启动子激活中的转录协同作用机制。
干扰素- β启动子作为组合转录调控的模型系统已被广泛研究。在病毒感染的细胞中,转录因子ATF-2、c-Jun、干扰素调节因子(IRF)-3、IRF-7和NF-kappaB以及共激活因子p300/CBP在这一启动子和其他启动子的激活中发挥关键作用。然而,目前尚不清楚为什么AP-1、IRF和Rel蛋白的大多数其他组合不能激活干扰素- β基因。在这里,我们探讨了不同的irf如何与其他因子合作来激活转录。首先,我们发现在未分化的胚胎癌细胞中,IRF-3或IRF-7的异位表达,而不是IRF-1,足以允许干扰素- β启动子的病毒依赖性激活。此外,IRF-3和IRF-7的活性受到启动子环境的强烈影响,IRF-7优先被招募到天然干扰素- β启动子中。我们在昆虫细胞中完全重建了该启动子的激活。最大的协同作用需要IRF-3和IRF-7,但不需要IRF-1,并且强烈依赖于p300/CBP的存在,即使这些共激活因子本身仅轻微影响每个因子的活性。这些结果表明,干扰素- β基因激活的特异性取决于独特的启动子环境和共激活因子作为结构因子所起的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信