Research Paper Volume 14, Issue 5 pp 2174—2193

Increased DNA methylation, cellular senescence and premature epigenetic aging in guinea pigs and humans with tuberculosis


Figure 1. Guinea pigs (Cavia porcellus) with TB exhibited DNA hypermethylation. (A) Infection experimental design; guinea pigs were infected with 100 CFU of Mtb CDC1551. Forty-five days later, spleen and lungs were removed with DNA methylation evaluated by RRBS. (B) Cavia with TB have DNA hypermethylation in lung and spleen when compared to uninfected controls. The number of genes with hypermethylation (red) or hypomethylation (blue) are plotted for each tissue (within 10kb from DMRs). (C) Genome browser (UCSC) view of a few key hypermethylated genes in Cavia with TB (red bars) as compared to non-infected “Saline” (blue bars). The bar plots represent methylation values from a scale of ‘0’ unmethylated (black horizontal axis) to ‘1’ fully methylated. Overall mean values combining both spleen and lungs are plotted. The Cavia scaffold position after alignment is indicated on top for each gene. (D) Shared and unique hypermethylated genes between lung and spleen. (E) Overlap of enriched pathways between Cavia spleen and lung (based on KEGG, Reactome, and Wikipathways) using hypermethylated genes. (F) Selected common pathways relevant to TB disease with their –log10 p-value of enrichment.