Combined Analysis of RRBS DNA Methylome and Transcriptome Reveal Novel Candidate Genes Related to Porcine Clostridium perfringens Type C-Induced Diarrhea

Abstract

Clostridium perfringens type C (Cp) is one of the principal microorganisms responsible for bacterial diarrhea in neonatal and pre-weaning piglets. To better understand the molecular effects of Cp infection, we performed a genome-wide comparison of the changes in DNA methylation and gene expression in Cp infected resistant and susceptible piglets. We characterized the pattern of changes in methylation and found 6485, 5968, and 6472 differentially methylated regions (DMRs) of piglets infected with Cp in IR vs. IC, IS vs. IC, and IS vs. IR groups, respectively. These methylation changes for genes mainly involved in immune and inflammatory responses, cell adhesion, and activation of transcription factors. Gene ontology and KEGG pathway analyses showed that the differentially methylated genes (DMGs) were associated with negative regulation of transcription, apoptotic processes, protein binding, and kinase activity. In addition, they were enriched in immunity-related pathways, such as MAPK signaling pathway, Toll-like receptor signaling pathway, and NF-kappa B signaling pathway. Integrative analysis identified 168, 198, and 7 mRNAs showing inverse correlations between methylation and expression with Cp infection. Altered DNA methylation and expression of various genes suggested their roles and potential functional interactions upon Cp infection, 14 immune-associated mRNAs with differential methylation and transcriptional repression were identified in IS vs. IR, commonly revealing that the differentially expressed genes (DEGs) LBP, TBX21, and LCN2 were likely involved in the piglets against Cp infection. The present results provide further insight into the DNA methylation epigenetic alterations of C. perfringens type C infected piglet ileum tissues, and may advance the identification of biomarkers and drug targets for predicting susceptibility to and controlling C. perfringens type C-induced piglet diarrhea.

The dynamic gene regulatory landscape of the mouse brain in response to sleep deprivation

“…Promoter hypo-methylation and gene body hyper-methylation are associated with increased gene expression (Ball et al, 2009) and occurs on very long (generations) (Gruzieva et al, 2019;Lowe et al, 2018) as well as short timescales (Elbere et al, 2018;Glahn et al, 2014;Luo et al, 2018;Xie et al, 2023). To understand the contribution of DNA methylation to the observed changes in OCR and gene expression, we conducted reduced representation bisulfite sequencing (RRBS) (Beck et al, 2022;Huang et al, 2022;Nakabayashi et al, 2023;Simpson et al, 2023) using CTX and SCN tissues from sham control and SD mice. We assessed genome-wide DNA methylation patterns and annotated differentially methylated regions (DMRs) by comparing a sliding window of 10 differentially methylated sites across brain region and/or condition.…”