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

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. 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. 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 and . These findings provide new insight into the primary role of CD4 and CD19 cells in MS.