Transcriptional outcomes and kinetic patterning of gene expression in response to NF-?B activation [RNA-seq]

Transcription factor NF-?B regulates cellular responses to environmental cues. For many stimuli NF-?B resides only transiently in the nucleus. Consequently, time-dependent transcriptional outputs are a fundamental feature of NF-?B activation. Here we identify mechanisms that direct kinetic patterns of NF-?B-dependent gene expression and transcriptional outcomes in response to a transient NF-?B-inducing stimulus in B cells. By combining RELA binding, RNA polymerase II (Pol II) recruitment, and perturbation of NF-?B activation, we demonstrate that kinetic differences amongst early- and late-activated RELA target genes can be understood based on chromatin configuration prior to cell activation and RELA-dependent priming, respectively. Additionally, we identified genes that were repressed by RELA activation and others that responded to RELA-activated transcription factors. Cumulatively, our studies define an NF-?B-responsive inducible gene cascade in activated B cells. Overall design: kinetic patterning of direct and indirect NF-?B targets