Integration of chromatin accessibility and gene expression data with cisREAD reveals a switch from PU.1/SPIB-driven to AP-1-driven gene regulation during B cell activation [ATAC-Seq]

Human B cell differentiation into antibody secreting plasma cells is a critical process in the adaptive immune response whose regulation at the genetic level remains incompletely understood. To reveal the temporal sequence of transcription factor driven cellular changes we generated chromatin accessibility (ATAC-seq) and gene expression (RNA-seq) data from the in vitro differentiation of human B cells into plasma cells. Data was gathered from three biological replicates using a published 13-day protocol of cytokine addition to drive differentiation. Using a new computational method, cisREAD (cis-Regulatory Elements Across Differentiation), we defined a core set of cis regulatory elements that are confidently linked to the dynamic binding of transcription factors and changes in gene expression. This confirmed known aspects of the differentiation process and revealed novel understanding, including a switch from PU.1/SPIB-driven to AP-1-driven genetic regulation associated with B cell activation. Overall design: Matched mRNA/ATAC-seq profiles of human naïve B-cells differentiated from day 0 to day 13 plasma cells, from 3 healthy donors.