RT Journal
A1 Pacis, Alain
A1 Tailleux, Ludovic
A1 Morin, Alexander M.
A1 Lambourne, John
A1 MacIsaac, Julia L.
A1 Yotova, Vania
A1 Dumaine, Anne
A1 Danckaert, Anne
A1 Luca, Francesca
A1 Grenier, Jean-Christophe
A1 Hansen, Kasper D.
A1 Gicquel, Brigitte
A1 Yu, Miao
A1 Pai, Athma
A1 He, Chuan
A1 Tung, Jenny
A1 Pastinen, Tomi
A1 Kobor, Michael S.
A1 Pique-Regi, Roger
A1 Gilad, Yoav
A1 Barreiro, Luis B.
T1 Bacterial infection remodels the DNA methylation landscape of human dendritic cells
JF Genome Research 
JO Genome Research 
YR 2015 
FD December 01 
VO 25 
IS 12 
SP 1801 
OP 1811 
DO 10.1101/gr.192005.115 
UL http://genome.cshlp.org/content/25/12/1801.abstract 
AB 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.