Bacterial infection remodels the DNA methylation landscape of human dendritic cells

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 (DCs) with a
live pathogenic bacteria is associated with rapid and active demethylation at
thousands of loci, independent of cell division. 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 demethylation rarely occurs at promoter regions
and instead localizes to distal enhancer elements, including those that
regulate the activation of key immune transcription factors. Active
demethylation is associated with extensive epigenetic remodeling, including the
gain of histone activation marks and increased chromatin accessibility, 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 to infection, even in nonproliferating cells.