389 Chromatin accessibility signatures in human blood CD4+ T and CD19+ B cells

Abstract

ObjectivesGenome-wide association studies (GWASs)suggest genetic variants’ regulatory effect in common diseases.To characterize the regulation in terms of chromatin accessibility in human blood CD4+ T and CD19+ B cells for skin immune/autoimmune diseases. MethodsWe sorted both human blood CD4+ T and CD19+ B cells by FACS in five healthy volunteers. We then performed ATAC-seq on BGISEQ500 with 50 bp paired-end read. We detected ATAC-seq features and performed, differential accessible analysis between T and B cells through generalized linear model.. We finally evaluated the enrichment effect of ATAC-seq features in GWAS findings of psoriasis, systemic lupus erythematosus (SLE), atopic dermatitis (AD), and vitiligo. Results We discovered 44,477 and 55,100 consensus ATAC-seq peaks in human blood CD4+ T and CD19+ B cells, respectively. We identified 46,737 cell-wide consensus peaks and characterized the difference of chromatin accessibility signatures between CD4+ T and CD19+ B cells. We found 12,511 of them are differentially accessible (FDR P < 0.05). These differentially accessible peaks (DAPs) suggest a role of several molecular pathways e.g intracellular signal transduction and immune response. We revealed that both T and B chromatin accessible features are enriched in psoriasis, SLE, and vitiligo associations (fold change > 2.1, P < 3.5E-5) but a modest enrichment effect of AD association in only T cells features (fold change=2.16, P = 0.02). Conclusions We characterized the chromatin accessibility signatures for both human blood CD4+ T and CD19+ B cells. The findings highlight their roles in diseases genetic associations.