Whole Genome Methylation Analysis Reveals Role of DNA Methylation in Cow’s Ileal and Ileal Lymph Node Responses to Mycobacterium avium subsp. paratuberculosis Infection

作者：Eveline M. Ibeagha‐Awemu, Nathalie Bissonnette, Suraj Bhattarai, Mengqi Wang, Pier-Luc Dudemaine, Stephanie McKay, Xin Zhao · 发表于：Frontiers in Genetics · 年份：2021 · DOI：10.3389/fgene.2021.797490 · 被引用次数：36 · 研究领域：Mycobacterium research and diagnosis、Cancer-related molecular mechanisms research、Helicobacter pylori-related gastroenterology studies

Johne’s Disease (JD), caused by Mycobacterium avium subsp paratuberculosis (MAP), is an incurable disease of ruminants and other animal species and is characterized by an imbalance of gut immunity. The role of MAP infection on the epigenetic modeling of gut immunity during the progression of JD is still unknown. This study investigated the DNA methylation patterns in ileal (IL) and ileal lymph node (ILLN) tissues from cows diagnosed with persistent subclinical MAP infection over a one to 4 years period. DNA samples from IL and ILLN tissues from cows negative (MAPneg) ( n = 3) or positive for MAP infection (MAPinf) ( n = 4) were subjected to whole genome bisulfite sequencing. A total of 11,263 and 62,459 differentially methylated cytosines (DMCs), and 1259 and 8086 differentially methylated regions (DMRs) (FDR<0.1) were found between MAPinf and MAPneg IL and ILLN tissues, respectively. The DMRs were found on 394 genes (denoted DMR genes) in the IL and on 1305 genes in the ILLN. DMR genes with hypermethylated promoters/5′UTR [3 (IL) and 88 (ILLN)] or hypomethylated promoters/5′UTR [10 (IL) and 25 (ILLN)] and having multiple functions including response to stimulus/immune response ( BLK, BTC, CCL21, AVPR1A, CHRNG, GABRA4, TDGF1 ), cellular processes ( H2AC20, TEX101, GLA, NCKAP5L, RBM27, SLC18A1, H2AC20BARHL2, NLGN3, SUV39H1, GABRA4, PPA1, UBE2D2 ) and metabolic processes ( GSTO2, H2AC20, SUV39H1, PPA1, UBE2D2 ) are potential DNA methylation candidate genes of MAP infecti...