The bovine alveolar macrophage DNA methylome is resilient to infection with Mycobacterium bovis

Alan Mark O’Doherty, Kevin Christophe Rue-Albrecht, David Andrew Magee, Simone Ahting, Rachelle Elizabeth Irwin, Thomas Jonathan Hall, John Arthur Browne, Nicolas Claude Nalpas, Colum Patrick Walsh, Stephen Vincent Gordon, Marcin Włodzimierz Wojewodzic, David Evan MacHugh

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    Abstract

    DNA methylation is pivotal in orchestrating gene expression patterns in various mammalian biological processes. Perturbation of the bovine alveolar macrophage (bAM) transcriptome, due to Mycobacterium bovis (M. bovis) infection, has been well documented; however, the impact of this intracellular pathogen on the bAM epigenome has not been determined. Here, whole genome bisulfite sequencing (WGBS) was used to assess the effect of M. bovis infection on the bAM DNA methylome. The methylomes of bAM infected with M. bovis were compared to those of non-infected bAM 24 hours post-infection (hpi). No differences in DNA methylation (CpG or non-CpG) were observed. Analysis of DNA methylation at proximal promoter regions uncovered >250 genes harbouring intermediately methylated (IM) promoters (average methylation of 33–66%). Gene ontology analysis, focusing on genes with low, intermediate or highly methylated promoters, revealed that genes with IM promoters were enriched for immune-related GO categories; this enrichment was not observed for genes in the high or low methylation groups. Targeted analysis of genes in the IM category confirmed the WGBS observation. This study is the first in cattle examining genome-wide DNA methylation at single nucleotide resolution in an important bovine cellular host-pathogen interaction model, providing evidence for IM promoter methylation in bAM.

    Original languageEnglish
    Article number1510 (2019)
    Number of pages15
    JournalScientific Reports
    Volume9
    Issue number1
    DOIs
    Publication statusPublished - 6 Feb 2019

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    O’Doherty, A. M., Rue-Albrecht, K. C., Magee, D. A., Ahting, S., Irwin, R. E., Hall, T. J., Browne, J. A., Nalpas, N. C., Walsh, C. P., Gordon, S. V., Wojewodzic, M. W., & MacHugh, D. E. (2019). The bovine alveolar macrophage DNA methylome is resilient to infection with Mycobacterium bovis. Scientific Reports, 9(1), [1510 (2019)]. https://doi.org/10.1038/s41598-018-37618-z