Bacterial Infection Remodels the DNA Methylation Landscape of Human Dendritic Cells (mRNA-Seq)

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: Transcriptional profiles (polyA+) of 6 non-infected and 6 MTB-infected dendritic cell samples.

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Pacis A, Tailleux L, Morin AM, Lambourne J, MacIsaac JL, Yotova V, Dumaine A, Danckaert A, Luca F, Grenier JC, Hansen KD, Gicquel B, Yu M, Pai A, He C, Tung J, Pastinen T, Kobor MS, Pique-Regi R, Gilad Y, Barreiro LB