NF-κB oscillations translate into functionally related patterns of gene expression

Several transcription factors (TFs) oscillate, periodically relocating between the cytoplasm and the nucleus. NF-kB, which plays key roles in inflammation and cancer, displaysoscillations whose biological advantage remains unclear. Recent work indicated that NF-kB displayssustained oscillations that can be entrained, that is, reach a persistent synchronized state through small periodic perturbations. We show here that for our GFP-p65 knock-in cells NF-kB behaves as a damped oscillator able to synchronize to a variety of periodic external perturbations with nomemory. We imposed synchronous dynamics to prove that transcription of NF-kB-controlled genes also oscillates, but mature transcript levels follow three distinct patterns. Two sets of transcripts accumulate fast or slowly, respectively. Another set, comprising chemokine and chemokinereceptor mRNAs, oscillates and resets at each new stimulus, with no memory of the past. We propose that TF oscillatory dynamics is a means of segmenting time to provide renewingopportunity windows for decision.