Bacterial Infection Remodels the DNA Methylation Landscape of Human Dendritic Cells

Overview

Journal Genome Res

Specialty Genetics

Date 2015 Sep 23

PMID 26392366

Citations 117

Authors

Alain Pacis

Ludovic Tailleux

Alexander M Morin

John Lambourne

Julia L MacIsaac

Vania Yotova

Anne Dumaine

Anne Danckaert

Francesca Luca

Jean-Christophe Grenier

Kasper D Hansen

Brigitte Gicquel

Miao Yu

Athma Pai

Chuan He

Jenny Tung

Tomi Pastinen

Michael S Kobor

Roger Pique-Regi

Yoav Gilad

Luis B Barreiro

Affiliations

Soon will be listed here.

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.

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