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Combined Analysis of DNA Methylome and Transcriptome Reveal Novel Candidate Genes Related to Porcine Escherichia coli F4ab/ac-Induced Diarrhea.

ABSTRACT: Enterotoxigenic Escherichia coli (ETEC) that express F4 (K88) fimbriae are the principal microorganisms responsible for bacterial diarrhea in neonatal and pre-weaning piglets. To better understand the molecular effects of ETEC F4ab/ac infection, we performed a genome-wide comparison of the changes in DNA methylation and gene expression in ETEC F4ab/ac infected porcine intestinal epithelial cells. We characterized the pattern of changes in methylation and found 3297 and 1593 differentially methylated regions in cells infected with F4ab and F4ac, respectively. Moreover, 606 and 780 differentially expressed genes (DEGs) in ETEC F4ab and F4ac infected cells were detected and these genes were highly enriched in immune/defense response related pathways. Integrative analysis identified 27 and 10 genes showing inverse correlations between promoter methylation and expression with ETEC F4ab/ac infection. Altered DNA methylation and expression of various genes suggested their roles and potential functional interactions upon ETEC F4ab/ac infection. Further functional analyses revealed that three DEGs (S100A9, SGO1, and ESPL1) in F4ab infected cells and three DEGs (MAP3K21, PAK6, and MPZL1) in F4ac infected cells are likely involved in the host cells response to ETEC infection. Our data provides further insight into the epigenetic and transcriptomic alterations of ETEC F4ab/ac infected porcine intestinal epithelial cells, and may advance the identification of biomarkers and drug targets for predicting susceptibility to and controlling ETEC F4ab/ac induced diarrhea.

SUBMITTER: Wang W

PROVIDER: S-EPMC7272597 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Combined Analysis of DNA Methylome and Transcriptome Reveal Novel Candidate Genes Related to Porcine <i>Escherichia coli</i> F4ab/ac-Induced Diarrhea.

Wang Wenwen W Zhou Chuanli C Tang Hui H Yu Ying Y Zhang Qin Q

Frontiers in cellular and infection microbiology 20200529

Enterotoxigenic <i>Escherichia coli</i> (ETEC) that express F4 (K88) fimbriae are the principal microorganisms responsible for bacterial diarrhea in neonatal and pre-weaning piglets. To better understand the molecular effects of ETEC F4ab/ac infection, we performed a genome-wide comparison of the changes in DNA methylation and gene expression in ETEC F4ab/ac infected porcine intestinal epithelial cells. We characterized the pattern of changes in methylation and found 3297 and 1593 differentially ...[more]

PMID: 32547963

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Project description:BackgroundEnterotoxigenic Escherichia coli (ETEC) that express the F4ab and F4ac fimbriae is a major contributor to diarrhoea outbreaks in the pig breeding industry, infecting both newborn and weaned piglets. Some pigs are resistant to this infection, and susceptibility is inherited as a simple dominant Mendelian trait. Indentifying the genetics behind this trait will greatly benefit pig welfare as well as the pig breeding industry by providing an opportunity to select against genetically susceptible animals, thereby reducing the number of diarrhoea outbreaks. The trait has recently been mapped by haplotype sharing to a 2.5 Mb region on pig chromosome 13, a region containing 18 annotated genes.FindingsThe coding regions of five candidate genes for susceptibility to ETEC F4ab/ac infection (TFRC, ACK1, MUC20, MUC4 and KIAA0226), all located in the 2.5 Mb region, were investigated for the presence of possible causative mutations. A total of 34 polymorphisms were identified in either coding regions or their flanking introns. The genotyping data for two of those were found to perfectly match the genotypes at the ETEC F4ab/ac locus, a G to C polymorphism in intron 11 of TFRC and a C to T silent polymorphism in exon 22 of KIAA0226. Transcriptional profiles of the five genes were investigated in a porcine tissue panel including various intestinal tissues. All five genes were expressed in intestinal tissues at different levels but none of the genes were found differentially expressed between ETEC F4ab/ac resistant and ETEC F4ab/ac susceptible animals in any of the tested tissues.ConclusionsNone of the identified polymorphisms are obvious causative mutations for ETEC F4ab/ac susceptibility, as they have no impact on the level of the overall mRNA expression nor predicted to influence the composition of the amino acids composition. However, we cannot exclude that the five tested genes are bona fide candidate genes for susceptibility to ETEC F4ab/ac infection since the identified polymorphism might affect the translational apparatus, alternative splice forms may exist and post translational mechanisms might contribute to disease susceptibility.

Dataset Information

Combined Analysis of DNA Methylome and Transcriptome Reveal Novel Candidate Genes Related to Porcine Escherichia coli F4ab/ac-Induced Diarrhea.

Publications

Combined Analysis of DNA Methylome and Transcriptome Reveal Novel Candidate Genes Related to Porcine <i>Escherichia coli</i> F4ab/ac-Induced Diarrhea.

Similar Datasets

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