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Bacterial Infection Remodels the DNA Methylation Landscape of Human Dendritic Cells

Alain Pacis, Ludovic Tailleux, John Lambourne, Vania Yotova, Anne Dumaine, Anne Danckaert, Francesca Luca, Jean-Christophe Grenier, Kasper D Hansen, Brigitte Gicquel, Miao Yu, Athma Pai, Jenny Tung, Chuan He, Tomi Pastinen, Roger Pique-Regi, Yoav Gilad, Luis B Barreiro
doi: https://doi.org/10.1101/016022
Alain Pacis
1CHU Sainte-Justine Research Center, Department of Genetics, Montreal, H3T1C5, Canada.
2University of Montreal, Department of Biochemistry, Montreal, H3T1J4, Canada.
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Ludovic Tailleux
3Institut Pasteur, Mycobacterial Genetics Unit, Paris, 75015, France.
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John Lambourne
4Génome Québec Innovation Centre, Department of Human Genetics, McGill University, Montréal, H3A0G1, Canada.
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Vania Yotova
1CHU Sainte-Justine Research Center, Department of Genetics, Montreal, H3T1C5, Canada.
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Anne Dumaine
1CHU Sainte-Justine Research Center, Department of Genetics, Montreal, H3T1C5, Canada.
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Anne Danckaert
5Institut Pasteur, Imagopole, Paris, 75015, France.
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Francesca Luca
6Wayne State University, Center for Molecular Medicine and Genetics and Department of Obstetrics and Gynecology, Detroit, MI, 48202.
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Jean-Christophe Grenier
1CHU Sainte-Justine Research Center, Department of Genetics, Montreal, H3T1C5, Canada.
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Kasper D Hansen
7Johns Hopkins Bloomberg School of Public Health, Department of Biostatistics and McKusick-Nathans Institute for Genetic Medicine, Baltimore, MD, 21205.
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Brigitte Gicquel
3Institut Pasteur, Mycobacterial Genetics Unit, Paris, 75015, France.
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Miao Yu
8University of Chicago, Department of Chemistry and Institute for Biophysical Dynamics, Chicago, IL, 60637.
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Athma Pai
9Department of Biology, Massachusetts Institute of Technology, United States.
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Jenny Tung
10Duke University, Departments of Evolutionary Anthropology and Biology and Duke Population Research Institute, Durham, NC, USA 27708.
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Chuan He
8University of Chicago, Department of Chemistry and Institute for Biophysical Dynamics, Chicago, IL, 60637.
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Tomi Pastinen
4Génome Québec Innovation Centre, Department of Human Genetics, McGill University, Montréal, H3A0G1, Canada.
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Roger Pique-Regi
6Wayne State University, Center for Molecular Medicine and Genetics and Department of Obstetrics and Gynecology, Detroit, MI, 48202.
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Yoav Gilad
11University of Chicago, Department of Human Genetics, Chicago, IL, 60637.
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  • For correspondence: luis.barreiro@umontreal.ca gilad@uchicago.edu
Luis B Barreiro
1CHU Sainte-Justine Research Center, Department of Genetics, Montreal, H3T1C5, Canada.
12University of Montreal, Department of Pediatrics, Montreal, H3T1J4, Canada.
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  • For correspondence: luis.barreiro@umontreal.ca gilad@uchicago.edu
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Abstract

DNA methylation is 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 pathogenic bacteria is associated with rapid changes in methylation at thousands of loci. Infection-induced changes in methylation occur primarily at distal enhancer elements, including those associated with the activation of key immune-transcription factors and genes involved in the crosstalk between DCs and adaptive immunity. Active demethylation is associated with extensive epigenetic remodeling and is strongly predictive of changes in the expression levels of nearby genes. Collectively, our observations show that rapid changes in methylation play a previously unappreciated role in regulating the transcriptional response of DCs to infection.

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Posted March 04, 2015.
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Bacterial Infection Remodels the DNA Methylation Landscape of Human Dendritic Cells
Alain Pacis, Ludovic Tailleux, John Lambourne, Vania Yotova, Anne Dumaine, Anne Danckaert, Francesca Luca, Jean-Christophe Grenier, Kasper D Hansen, Brigitte Gicquel, Miao Yu, Athma Pai, Jenny Tung, Chuan He, Tomi Pastinen, Roger Pique-Regi, Yoav Gilad, Luis B Barreiro
bioRxiv 016022; doi: https://doi.org/10.1101/016022
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Bacterial Infection Remodels the DNA Methylation Landscape of Human Dendritic Cells
Alain Pacis, Ludovic Tailleux, John Lambourne, Vania Yotova, Anne Dumaine, Anne Danckaert, Francesca Luca, Jean-Christophe Grenier, Kasper D Hansen, Brigitte Gicquel, Miao Yu, Athma Pai, Jenny Tung, Chuan He, Tomi Pastinen, Roger Pique-Regi, Yoav Gilad, Luis B Barreiro
bioRxiv 016022; doi: https://doi.org/10.1101/016022

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