BACKGROUND Aberrant DNA methylation is induced by aging and chronic inflammation in normal tissues. The induction by inflammation is widely recognized as acceleration of age-related methylation. However, few studies addressed target genomic regions and the responsible factors in a genome-wide manner. Here, we analyzed methylation targets by aging and inflammation, taking advantage of the potent methylation induction in human gastric mucosa by Helicobacter pylori infection-triggered inflammation. RESULTS DNA methylation microarray analysis of 482,421 CpG probes, grouped into 270,249 genomic blocks, revealed that high levels of methylation were induced in 44,461 (16.5%) genomic blocks by inflammation, even after correction of the influence of leukocyte infiltration. A total of 61.8% of the hypermethylation was acceleration of age-related methylation while 21.6% was specific to inflammation. Regions with H3K27me3 were frequently hypermethylated both by aging and inflammation. Basal methylation levels were essential for age-related hypermethylation while even regions with little basal methylation were hypermethylated by inflammation. When limited to promoter CpG islands, being a microRNA gene and high basal methylation levels strongly enhanced hypermethylation while H3K27me3 strongly enhanced inflammation-induced hypermethylation. Inflammation was capable of overriding active transcription. In young gastric mucosae, genes with high expression and frequent mutations in gastric cancers were more frequently methylated than in old ones. CONCLUSIONS Methylation by inflammation was not simple acceleration of age-related methylation. Targets of aberrant DNA methylation were different between young and old gastric mucosae, and driver genes were preferentially methylated in young gastric mucosa.

中文翻译：

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通过衰老和慢性炎症实现不同的DNA甲基化目标：使用感染了幽门螺杆菌的胃粘膜进行的一项初步研究。

背景技术异常DNA甲基化是由正常组织中的衰老和慢性炎症引起的。炎症诱导被广泛认为是与年龄有关的甲基化的加速。然而，很少有研究以全基因组的方式解决靶基因组区域和相关因素。在这里，我们利用衰老和炎症分析了甲基化靶标，利用了幽门螺杆菌感染触发的炎症在人胃粘膜中的强甲基化诱导作用。结果对482,421个CpG探针进行的DNA甲基化微阵列分析（分为270,249个基因组模块）显示，即使在校正了白细胞浸润的影响后，炎症也会在44,461个（16.5％）基因组模块中诱导高水平的甲基化。总共61个。8％的高甲基化是与年龄有关的甲基化的加速，而21.6％的炎症是特异性的。具有H3K27me3的区域经常因衰老和发炎而甲基化。基础甲基化水平对于与年龄相关的甲基化至关重要，而即使基础甲基化很少的区域也会因炎症而甲基化。当仅限于启动子CpG岛时，是microRNA基因和高的基础甲基化水平强烈增强了高甲基化，而H3K27me3则强烈增强了炎症诱导的高甲基化。炎症能够覆盖主动转录。在年轻的胃粘膜中，高表达和频繁突变的基因在胃癌中的甲基化频率比老基因更高。结论炎症引起的甲基化不是与年龄相关的甲基化的简单加速。年轻和老胃黏膜之间异常DNA甲基化的目标是不同的，并且驱动基因在年轻胃黏膜中优先被甲基化。