A novel virus-inducible enhancer of the interferon-β gene with tightly linked promoter and enhancer activities.
A novel virus-inducible enhancer of the interferon-β gene with tightly linked promoter and enhancer activities.
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DOI：
10.1093/nar/gku1018
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发表时间：
2014-11-10
影响因子：
14.9
通讯作者：
Kim TH
中科院分区：
文献类型：
--
作者：
Banerjee AR;Kim YJ;Kim TH
长程转录增强子是基因组调控体系的关键组成部分。最近的研究已经确定了从这些增强子发出的双向转录的RNA，称为eRNAs。然而，目前尚不清楚Erna的生产与增强子活性有多紧密的联系。通过系统地寻找与干扰素-β基因相互作用的长程元件，我们已经确定了一种新的增强子，我们将其命名为L2，它调节干扰素-β的表达。我们已经通过分析表观基因组图谱、转录因子关联、新生RNA产生和报告实验中的活性来证明其病毒诱导的增强子活性。这种增强子表现出紧密相连的病毒诱导的增强子和双向启动子的活性，这在很大程度上依赖于保守的干扰素刺激反应元件，并强烈地产生病毒诱导的eRNA。值得注意的是，它的增强子和启动子活性在报告分析中完全保留，即使在完全消除其相关的Erna序列时也是如此。最后，我们证明了L2通过siRNA敲除eRNAs和在BAC转染实验中删除L2来调节IFNB1的表达。因此，L2是一种新的调节IFNB1的增强子，其eRNAs在体内发挥着显著的活性，这与荧光素酶报告分析中概述的那些活性不同。
Long-range enhancers of transcription are a key component of the genomic regulatory architecture. Recent studies have identified bi-directionally transcribed RNAs emanating from these enhancers known as eRNAs. However, it remains unclear how tightly coupled eRNA production is with enhancer activity. Through our systematic search for long-range elements that interact with the interferon-β gene, a model system for studying inducible transcription, we have identified a novel enhancer, which we have named L2 that regulates the expression of interferon-β. We have demonstrated its virus-inducible enhancer activity by analyzing epigenomic profiles, transcription factor association, nascent RNA production and activity in reporter assays. This enhancer exhibits intimately linked virus-inducible enhancer and bidirectional promoter activity that is largely dependent on a conserved Interferon Stimulated Response Element and robustly generates virus inducible eRNAs. Notably, its enhancer and promoter activities are fully retained in reporter assays even upon a complete elimination of its associated eRNA sequences. Finally, we show that L2 regulates IFNB1 expression by siRNA knockdown of eRNAs, and the deletion of L2 in a BAC transfection assay. Thus, L2 is a novel enhancer that regulates IFNB1 and whose eRNAs exert significant activity in vivo that is distinct from those activities recapitulated in the luciferase reporter assays.
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影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
DOI：
10.1126/science.1162327
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Badis G;Berger MF;Philippakis AA;Talukder S;Gehrke AR;Jaeger SA;Chan ET;Metzler G;Vedenko A;Chen X;Kuznetsov H;Wang CF;Coburn D;Newburger DE;Morris Q;Hughes TR;Bulyk ML
通讯作者：
Bulyk ML
影响因子：
4.8
作者：
Chien, Richard;Zeng, Weihua;Yokomori, Kyoko
通讯作者：
Yokomori, Kyoko
DOI：
10.1038/nrg3454
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA