Epigenetic Basis for the Establishment of Ruminal Tissue-Specific Functions

While DNA methylation in other tissues can be approximated through model species, the dynamic distribution and regulatory significance of DNA methylation in the rumen, a unique organ in ruminant, remain largely unknown. Here, we employed whole-genome bisulfite sequencing (WGBS), transcriptomics, and histone modification data to compare fetal and adult stages of bovine rumen with other tissues, including pluripotent stem cells (PSCs) approximating pre-implantation embryos. We found extensive methylation differences, including CG methylation (mCG) and non-CG methylation (mCH; H represents A, C and T) between the rumen at fetal and adult stages and other tissues and PSCs. These differentially methylated regions (DMRs) are closely associated with other epigenetic regulatory components, such as transcription factors (TFs) and histone modifications. These DMRs can also combine to form large hypo CG-DMRs to regulate a cluster of functionally related genes. We elucidated the reasons for morphological and functional differences between fetal and adult rumen at the epigenetic level and the interactions between epigenetic modifications and gene expression. This study highlights the differences in methylation patterns between the rumen and other tissues during development and the role of DNA methylation in controlling gene expression and establishing tissue-specific functions.