A genomic portrait of the genetic architecture and regulatory impact of microRNA expression in response to infection.
A genomic portrait of the genetic architecture and regulatory impact of microRNA expression in response to infection.
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DOI：
10.1101/gr.161471.113
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发表时间：
2014-05
期刊：
影响因子：
7
通讯作者：
Quintana-Murci L
中科院分区：
文献类型：
--
作者：
Siddle KJ;Deschamps M;Tailleux L;Nédélec Y;Pothlichet J;Lugo-Villarino G;Libri V;Gicquel B;Neyrolles O;Laval G;Patin E;Barreiro LB;Quintana-Murci L
microRNAs（miRNAs）是基因表达的重要调控因子，其在多种生物学过程中的作用，包括宿主的抗菌防御，越来越多地被描述。与其多样的功能效应一致，miRNA表达是高度依赖于环境的，并且在细胞活化时显示出显著的变化。然而，响应于外部刺激的miRNA表达的遗传控制以及在群体水平上这种扰动对miRNA介导的调控网络的影响仍有待确定。在这里，我们评估了结核分枝杆菌感染后miRNA表达的变化，并绘制了一组健康个体树突状细胞的表达数量性状基因座（eQTL）。全基因组表达谱显示，约40%的miRNA在感染后差异表达。我们发现3%的miRNAs的表达是由邻近的遗传因子控制的，这些遗传因子富含与主动转录相关的启动子特异性组蛋白修饰。值得注意的是，我们确定了两个感染特异性反应eQTL，miR-326和miR-1260，提供了一个初步的评估基因型-环境相互作用对miRNA分子表型的影响。此外，我们发现感染与miRNA和mRNA表达水平之间的全基因组关系的显著重塑相一致。这一观察结果，加上使用miR-29 a模型的实验数据，揭示了一组miRNA在细胞感染反应中的作用。总的来说，这项研究增加了我们对感染后miRNA表达的遗传结构的理解，并突出了改变miRNA表达对细胞转录景观的广泛影响。
MicroRNAs (miRNAs) are critical regulators of gene expression, and their role in a wide variety of biological processes, including host antimicrobial defense, is increasingly well described. Consistent with their diverse functional effects, miRNA expression is highly context dependent and shows marked changes upon cellular activation. However, the genetic control of miRNA expression in response to external stimuli and the impact of such perturbations on miRNA-mediated regulatory networks at the population level remain to be determined. Here we assessed changes in miRNA expression upon Mycobacterium tuberculosis infection and mapped expression quantitative trait loci (eQTL) in dendritic cells from a panel of healthy individuals. Genome-wide expression profiling revealed that ∼40% of miRNAs are differentially expressed upon infection. We find that the expression of 3% of miRNAs is controlled by proximate genetic factors, which are enriched in a promoter-specific histone modification associated with active transcription. Notably, we identify two infection-specific response eQTLs, for miR-326 and miR-1260, providing an initial assessment of the impact of genotype-environment interactions on miRNA molecular phenotypes. Furthermore, we show that infection coincides with a marked remodeling of the genome-wide relationships between miRNA and mRNA expression levels. This observation, supplemented by experimental data using the model of miR-29a, sheds light on the role of a set of miRNAs in cellular responses to infection. Collectively, this study increases our understanding of the genetic architecture of miRNA expression in response to infection, and highlights the wide-reaching impact of altering miRNA expression on the transcriptional landscape of a cell.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
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影响因子：
30.5
作者：
Du, Changsheng;Liu, Chang;Pei, Gang
通讯作者：
Pei, Gang
DOI：
10.1126/science.1179050
发表时间：
2009-10-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Amit I;Garber M;Chevrier N;Leite AP;Donner Y;Eisenhaure T;Guttman M;Grenier JK;Li W;Zuk O;Schubert LA;Birditt B;Shay T;Goren A;Zhang X;Smith Z;Deering R;McDonald RC;Cabili M;Bernstein BE;Rinn JL;Meissner A;Root DE;Hacohen N;Regev A
通讯作者：
Regev A
影响因子：
64.5
作者：
Chevrier N;Mertins P;Artyomov MN;Shalek AK;Iannacone M;Ciaccio MF;Gat-Viks I;Tonti E;DeGrace MM;Clauser KR;Garber M;Eisenhaure TM;Yosef N;Robinson J;Sutton A;Andersen MS;Root DE;von Andrian U;Jones RB;Park H;Carr SA;Regev A;Amit I;Hacohen N
通讯作者：
Hacohen N