Nanopore sequencing identifies differentially methylated genes in the central nervous system in experimental autoimmune encephalomyelitis

Abstract

Multiple Sclerosis (MS) is a chronic autoimmune-mediated demyelinating disease of the central nervous system (CNS) that might be triggered by aberrant epigenetic changes in the genome. DNA methylation is the most studied epigenetic mechanism that participates in MS pathogenesis. However, the overall methylation level in the CNS of MS patients remains elusive. We used direct long-read nanopore DNA sequencing and characterized the differentially methylated genes in the brain from mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We identified 163 hypomethylated promoters and 327 hypermethylated promoters. These genomic alterations were linked to various biological processes including metabolism, immune responses, neural activities, and mitochondrial dynamics, all of which are vital for EAE development. Our results indicate a great potential of nanopore sequencing in identifying genomic DNA methylation in EAE and provide important guidance for future studies investigating the MS/EAE pathology.

Keywords: DNA methylation; Differentially methylated genes; Experimental autoimmune encephalomyelitis; Multiple sclerosis; mtDNA methylation.