Bacterial Infection Remodels the DNA Methylation Landscape of Human Dendritic Cells (ATAC-Seq). Homo sapiens

DNA methylation is an epigenetic mark thought to be robust to environmental perturbations on a short time scale. Here, we challenge that view by demonstrating that the infection of human dendritic cells with a live pathogenic bacteria is associated with rapid changes in methylation levels at thousands of loci. We performed an integrated analysis of data on genome-wide DNA methylation, histone mark patterns, chromatin accessibility, and gene expression, before and after infection. We found that infection-induced changes in methylation rarely occur at promoter regions and instead localize to distal enhancer elements. Active demethylation is associated with extensive epigenetic remodeling, including the gain of histone activation marks and the induction of enhancer RNAs, and is strongly predictive of changes in the expression levels of nearby genes. Collectively, our observations show that active, rapid changes in DNA methylation in enhancers play a previously unappreciated role in regulating the transcriptional response of immune cells to infection. Overall design: Chromatin accessibility profiles of one non-infected and one MTB-infected dendritic cell sample.

DNA甲基化（DNA methylation）是一类表观遗传标记，既往研究认为其在短时间尺度上不易受环境扰动影响。本研究通过证实活致病性细菌感染人类树突状细胞可引发数千个基因座的甲基化水平快速变化，对这一固有认知提出了挑战。我们对感染前后的全基因组DNA甲基化、组蛋白修饰模式、染色质开放状态以及基因表达数据进行了整合分析。研究发现，感染诱导的甲基化变化极少发生于启动子区域，而是主要定位于远端增强子元件。主动去甲基化过程与广泛的表观遗传重塑密切相关，包括组蛋白激活修饰的获得与增强子RNA的诱导，且可显著预测邻近基因的表达水平变化。综上，本研究结果表明，增强子区域内DNA甲基化的主动快速变化，在免疫细胞应对感染的转录应答调控中发挥了此前未被重视的重要作用。实验设计：对1份未感染树突状细胞样本与1份结核分枝杆菌（MTB）感染的树突状细胞样本进行染色质开放状态谱型分析。