Deep characterization of paired chromatin and transcriptomes in four immune cell types from multiple sclerosis...

Background: The putative involvement of chromatin states in multiple sclerosis (MS) is thus far unclear. Here we determined the association of chromatin-accessibility with concurrent genetic, epigenetic and transcriptional events. Material & methods: We generated paired assay for transposase-accessible chromatin sequencing and RNA-sequencing profiles from sorted blood immune CD4⁺ and CD8⁺ T cells, CD14⁺ monocytes and CD19⁺ B cells from healthy controls (HCs) and MS patients. Results: We identified differentially accessible regions between MS patients and HCs, primarily in CD4⁺ and CD19⁺. CD4⁺ regions were enriched for MS-associated single nucleotide polymorphisms and differentially methylated loci. In the vicinity of differentially accessible regions of CD4⁺ cells, 42 differentially expressed genes were identified. The top two dysregulated genes identified in this multilayer analysis were CCDC114 and SERTAD1. Conclusion: These findings provide new insight into the primary role of CD4⁺ and CD19⁺ cells in MS.