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

Fernandes SJ, Ericsson M, Khademi M, Jagodic M, Olsson T, Gomez-Cabrero D, Kockum I, Tegnér J

Epigenomics 13 (20) 1607-1618 [2021-10-00; online 2021-10-22]

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.

PubMed 34676774

DOI 10.2217/epi-2021-0205

Crossref 10.2217/epi-2021-0205