Imaging and single cell sequence analyses of super-enhancer activation mediated by NF-kB in B cells

NF-kB signaling pathway plays important roles in cell fate determination of a variety of cells and is involved in activation of super-enhancers, long clusters of enhancers for transcriptional regulation. Here we show using fluorescence imaging and single cell transcriptome and chromatin accessibility analyses that NF-kB subunit RelA nuclear foci formation and single cell gene expression exhibits super-enhancer-like properties in anti-IgM stimulated B cells, contributing to bimodal transcriptional response and enhanced heterogeneity. Furthermore, we found that predicted cis-regulatory interacting genomic regions from chromatin co-accessibility data can be a predictor for transcriptional heterogeneity. Our study indicates that NF-kB super-enhancer formation is important for the expression of NF-kB target genes and the amplification of transcriptional heterogeneity in response to environmental stimuli in B cells.