Mapping epigenetic changes to the host cell genome induced by Burkholderia pseudomallei reveals pathogen-specific and pathogen-generic signatures of infection.
Mapping epigenetic changes to the host cell genome induced by Burkholderia pseudomallei reveals pathogen-specific and pathogen-generic signatures of infection.
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DOI：
10.1038/srep30861
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发表时间：
2016-08-03
影响因子：
4.6
通讯作者：
Titball RW
中科院分区：
文献类型：
--
作者：
Cizmeci D;Dempster EL;Champion OL;Wagley S;Akman OE;Prior JL;Soyer OS;Mill J;Titball RW
微生物感染后宿主细胞发生表观遗传变化的可能性已被广泛提出，但很少有实例报道。我们评估了人巨噬细胞样U937细胞感染假马氏伯克氏菌（一种细胞内细菌病原体和人类类melidosis的病原体）后DNA甲基化的全基因组模式。我们的分析揭示了宿主细胞DNA甲基化的显著变化，在宿主细胞基因组的多个CpG位点，感染后。感染诱导的差异甲基化探针（iDMPs）显示DNA甲基化变化最大，被发现位于参与炎症反应、细胞内信号传导、细胞凋亡和病原体诱导信号传导的基因附近。将我们的数据与已报道的结核分枝杆菌感染细胞的甲基化变化进行比较，揭示了差异甲基化基因的共性，包括参与T细胞反应的基因（BCL11B、fox01、KIF13B、PAWR、SOX4、SYK）、肌动蛋白细胞骨架组织（ACTR3、CDC42BPA、DTNBP1、FERMT2、PRKCZ、RAC1）和细胞因子产生（FOXP1、IRF8、MR1）。总的来说，我们的研究结果表明，感染后甲基组发生了致病性特异性和致病性共同的变化。
The potential for epigenetic changes in host cells following microbial infection has been widely suggested, but few examples have been reported. We assessed genome-wide patterns of DNA methylation in human macrophage-like U937 cells following infection with Burkholderia pseudomallei, an intracellular bacterial pathogen and the causative agent of human melioidosis. Our analyses revealed significant changes in host cell DNA methylation, at multiple CpG sites in the host cell genome, following infection. Infection induced differentially methylated probes (iDMPs) showing the greatest changes in DNA methylation were found to be in the vicinity of genes involved in inflammatory responses, intracellular signalling, apoptosis and pathogen-induced signalling. A comparison of our data with reported methylome changes in cells infected with M. tuberculosis revealed commonality of differentially methylated genes, including genes involved in T cell responses (BCL11B, FOXO1, KIF13B, PAWR, SOX4, SYK), actin cytoskeleton organisation (ACTR3, CDC42BPA, DTNBP1, FERMT2, PRKCZ, RAC1), and cytokine production (FOXP1, IRF8, MR1). Overall our findings show that pathogenic-specific and pathogen-common changes in the methylome occur following infection.