# Construction of a DNA Methylation Map of Argali Hybrid Sheep During Mo Infection

## TL;DR

This study maps DNA methylation changes in argali hybrid sheep infected with a pneumonia-causing bacteria, revealing how epigenetic shifts may contribute to disease.

## Contribution

The paper provides the first genome-wide DNA methylation profile of argali hybrid sheep lungs during Mycoplasma ovipneumoniae infection.

## Key findings

- Mo infection causes global hypermethylation in sheep lungs, with 3691 differentially methylated regions identified.
- Methylation changes are concentrated in immune-related genes, potentially suppressing immune responses.
- Validation confirms methylation status of specific genes like SGK1 and GILT, linking methylation to gene expression.

## Abstract

The DNA methylation landscape in the lungs of argali hybrid sheep infected with Mycoplasma ovipneumoniae (Mo) remains poorly characterized. This study aimed to profile genome-wide DNA methylation using reduced representation bisulfite sequencing (RRBS) and to validate key genes using bisulfite sequencing PCR (BSP), methylation-specific PCR (MSP), and quantitative MSP (QMSP). The results revealed a significant increase in global mCG methylation in -infected lungs. RRBS identified 3691 differentially methylated regions (DMRs), 66.2% of which were hypermethylated. Methylation levels were highest in gene bodies/downstream regions and lowest in promoters/5′ untranslated regions. Differentially methylated genes (DMGs) were enriched in immune–inflammatory pathways (e.g., antigen presentation, B-cell receptor signaling, Th17 differentiation) and, to a lesser extent, neural signaling pathways. BSP confirmed the methylation status of hypermethylated (KHDC3L, GILT, OVAR-DRB1, SGK1, ADAM17) and hypomethylated (EFCAB11, AP1B1, TATDN1) DMGs. Independent validation by MSP and QMSP further supported the hypermethylation of SGK1 and GILT in both lung tissue and alveolar macrophages. Quantitative reverse-transcription PCR showed that promoter hypermethylation of KHDC3L, GILT, SGK1, and ADAM17 was associated with transcriptional downregulation, while hypomethylation of AP1B1 correlated with upregulation. In summary, Mo infection induces genome-wide hypermethylation reprogramming that dysregulates key immune-related genes, highlighting potential epigenetic mechanisms in the pathogenesis of mycoplasmal pneumonia.