Bacterial infection remodels the DNA methylation landscape of human dendritic cells
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Pacis-2015-Bacterial infection.pdf
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Author(s)
Pacis, Alain
Tailleux, Ludovic
Morin, Alexander M.
Lambourne, John
MacIsaac, Julia L.
Yotova, Vania
Dumaine, Anne
Danckaert, Anne
Luca, Francesca
Grenier, Jean-Christophe
Date Issued
September 2015
Journal
Genome Research
Publisher
Cold Spring Harbor Laboratory Press
Citation
Pacis, Alain, Ludovic Tailleux, Alexander M. Morin, John Lambourne, Julia L. MacIsaac, Vania Yotova, Anne Dumaine, et al. “Bacterial Infection Remodels the DNA Methylation Landscape of Human Dendritic Cells.” Genome Res. 25, no. 12 (September 21, 2015): 1801–1811.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1101/gr.192005.115
