Methylome and transcriptome data integration reveals aberrantly regulated genes in equine sarcoids

DNA methylation is a key mechanism in transcription regulation, and aberrant methylation is a common and important mechanism in tumor initiation, maintenance, and progression. To find genes that are aberrantly regulated by altered methylation in horse sarcoids, we used reduced representation bisulfite sequencing (RRBS) accompanied by RNA sequencing (RNA-Seq) for methylome (whole genome DNA methylation sequencing) and transcriptome profiling, respectively. We found that the DNA methylation level was generally lower in lesion samples than in controls. In the analyzed samples, a total of 14,692 differentially methylated sites (DMSs) in the context of CpG (where cytosine and guanine are separated by a phosphate), and 11,712 differentially expressed genes (DEGs) were identified. The integration of the methylome and transcriptome data suggests that aberrant DNA methylation may be involved in the deregulation of expression of the 493 genes in equine sarcoid. Furthermore, enrichment analysis of the genes demonstrated the activation of multiple molecular pathways related to extracellular matrix (ECM), oxidative phosphorylation (OXPHOS), immune response, and disease processes that can be related to tumor progression. The results provide further insight into the epigenetic alterations in equine sarcoids and provide a valuable resource for follow-up studies to identify biomarkers for predicting susceptibility to this common condition in horses. (c) 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

DNA methylation is a key mechanism in regulating gene expression, and aberrant methylation plays an important role in tumor development. In this study, we used RRBS and RNA-Seq to analyze the methylome and transcriptome of horse sarcoids. We identified thousands of differentially methylated sites and differentially expressed genes, suggesting the involvement of aberrant DNA methylation in the deregulation of gene expression in equine sarcoids. Further enrichment analysis revealed the activation of molecular pathways related to tumor progression. These findings provide valuable insights into the epigenetic alterations in equine sarcoids and can be used for future studies on biomarker identification.