Summary
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.
Highlights
Comprehensive analysis of bovine alveolar macrophage (bAM) transcriptome and chromatin architecture revealed Mycobacterium bovis (M. bovis) induces genome-wide chromatin remodelling in bAM
M. bovis induces transcriptional changes of immune response genes, associated with changes of histone modifications and RNA Polymerase II (PolII) occupancy
GWAS integration of our ChIP study enabled the identification of important SNPs for bovine tuberculosis (bTB) susceptibility
Footnotes
↵6 Lead contact: Thomas Jonathan Hall, Thomas.Hall{at}ucdconnect.ie, ++353857168930
Grant Support:
This study was supported by Science Foundation Ireland (SFI) Investigator Programme Awards (grant nos. SFI/08/IN.1/B2038 and SFI/15/IA/3154); a European Union Framework 7 Project Grant (no: KBBE-211602-MACROSYS); and an EU H2020 COST Action short term scientific mission (STSM) grant (reference code: COST-STSM-ECOST-STSM-CA15112-050317-081648).