Bacterial infection remodels the DNA methylation landscape of human dendritic cells.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • December 2015

Published In

Volume / Issue

  • 25 / 12

Start / End Page

  • 1801 - 1811

PubMed ID

  • 26392366

Pubmed Central ID

  • 26392366

Electronic International Standard Serial Number (EISSN)

  • 1549-5469

International Standard Serial Number (ISSN)

  • 1088-9051

Digital Object Identifier (DOI)

  • 10.1101/gr.192005.115

Language

  • eng