Bacterial infection remodels the DNA methylation landscape of human dendritic cells

Alain Pacis, Ludovic Tailleux, Alexander M. Morin, John Lambourne, Julia L. MacIsaac, Vania Yotova, Anne Dumaine, Anne Danckært, Francesca Luca, Jean Christophe Grenier, Kasper D. Hansen, Brigitte Gicquel, Miao Yu, Athma Pai, Chuan He, Jenny Tung, Tomi Pastinen, Michæl S. Kobor, Roger Pique-Regi, Yoav GiladLuis B. Barreiro

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1801-1811
Number of pages11
JournalGenome research
Volume25
Issue number12
DOIs
StatePublished - Dec 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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  • Cite this

    Pacis, A., Tailleux, L., Morin, A. M., Lambourne, J., MacIsaac, J. L., Yotova, V., Dumaine, A., Danckært, A., Luca, F., Grenier, J. C., Hansen, K. D., Gicquel, B., Yu, M., Pai, A., He, C., Tung, J., Pastinen, T., Kobor, M. S., Pique-Regi, R., ... Barreiro, L. B. (2015). Bacterial infection remodels the DNA methylation landscape of human dendritic cells. Genome research, 25(12), 1801-1811. https://doi.org/10.1101/gr.192005.115