TY  - JOUR
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
Y1  - 2015/12/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1801 
EP  - 1811 
DO  - 10.1101/gr.192005.115 
VL  - 25 
IS  - 12 
UR  - http://genome.cshlp.org/content/25/12/1801.abstract 
N2  - 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. 
ER  -