@article{cc26648257e742878c1c4270fc463753,
title = "Bacterial infection remodels the DNA methylation landscape of human dendritic cells",
abstract = "DNAmethylation 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.",
author = "Alain Pacis and Ludovic Tailleux and Morin, {Alexander M.} and John Lambourne and MacIsaac, {Julia L.} and Vania Yotova and Anne Dumaine and Anne Danck{\ae}rt and Francesca Luca and Grenier, {Jean Christophe} and Hansen, {Kasper D.} and Brigitte Gicquel and Miao Yu and Athma Pai and Chuan He and Jenny Tung and Tomi Pastinen and Kobor, {Mich{\ae}l S.} and Roger Pique-Regi and Yoav Gilad and Barreiro, {Luis B.}",
note = "Funding Information: We thank B. Jabri, V. Abadie, and J.F. Brinkworth for helpful discussions and comments on the manuscript; K. Michelini and C. Chavarria for technical assistance running the sequencer; G. Stewart for the gift of the MTB strain used in this study; and P. Roux for advice on the confocal microscopy. We thank Calcul Quebec and Compute Canada for managing and providing access to the supercomputer Briaree from the University of Montreal. This study was funded by National Institutes of Health (NIH) Grant AI087658 (to Y.G. and L.T.), by grants from the Canadian Institutes of Health Research (301538 and 232519), the Human Frontiers Science Program (CDA-00025/2012), and the Canada Research Chairs Program (950-228993) (to L.B.B.), by the Canadian Institutes of Health Research/Canadian Epigenetics, Environment and Health Research Consortium (to T.P.), and by the NIH grant HG006827 (to C.H.). M.S.K. is a Canada Research Chair in Social Epigenetics and a Senior Fellow of the Canadian Institute for Advanced Research. A.P. was supported by a fellowship from the R{\'e}seau de M{\'e}decine G{\'e}n{\'e}tique Appliqu{\'e}e (RMGA). Publisher Copyright: {\textcopyright} 2015 Robin et al.",
year = "2015",
month = dec,
doi = "10.1101/gr.192005.115",
language = "English (US)",
volume = "25",
pages = "1801--1811",
journal = "Genome Research",
issn = "1088-9051",
publisher = "Cold Spring Harbor Laboratory Press",
number = "12",
}