Transcriptional outcomes and kinetic patterning of gene expression in response to NF-κB activation [ChIP-seq]

Transcription factor NF-κB regulates cellular responses to environmental cues. For many stimuli NF-κB resides only transiently in the nucleus. Consequently, time-dependent transcriptional outputs are a fundamental feature of NF-κB activation. Here we identify mechanisms that direct kinetic patterns of NF-κB-dependent gene expression and transcriptional outcomes in response to a transient NF-κB-inducing stimulus in B cells. By combining RELA binding, RNA polymerase II (Pol II) recruitment, and perturbation of NF-κB 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-κB-responsive inducible gene cascade in activated B cells. kinetic patterning of direct and indirect NF-κB targets