Alveolar macrophage chromatin is modified to orchestrate host response to Mycobacterium bovis infection

Mycobacterium bovis, the causative pathogen of bovine tuberculosis (bTB), induces extensive reprogramming of the macrophage transcriptome during infection. To identify key transcriptional changes in infected bovine alveolar macrophages (bAM), we have performed both gene expression (RNA-seq) and epigenomic (ChIP-seq) analyses using two key histone modification marks associated with activation (H3K4me3) and repression (H3K27me3). Together with RNA polymerase II (PolII) occupancy data, we show that reprogramming of the bAM transcriptome after M. bovis infection affects key immune response genes. Identification of these genes also facilitated integration of GWAS data, which identified genomic regions and SNPs significantly associated with resilience to infection with M. bovis in cattle.\n\nHighlightsO_LIComprehensive analysis of bovine alveolar macrophage (bAM) transcriptome and chromatin architecture revealed Mycobacterium bovis (M. bovis) induces genome-wide chromatin remodelling in bAM\nC_LIO_LIM. bovis induces transcriptional changes of immune response genes, associated with changes of histone modifications and RNA Polymerase II (PolII) occupancy\nC_LIO_LIGWAS integration of our ChIP study enabled the identification of important SNPs for bovine tuberculosis (bTB) susceptibility\nC_LI\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=69 SRC=\"FIGDIR/small/520098_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (19K):\norg.highwire.dtl.DTLVardef@1946689org.highwire.dtl.DTLVardef@1d7c0aborg.highwire.dtl.DTLVardef@1aa5c1forg.highwire.dtl.DTLVardef@1860ea5_HPS_FORMAT_FIGEXP M_FIG C_FIG