NF-κB oscillations translate into functionally related patterns of gene expression.
Samuel ZambranoIlario De TomaArianna PifferMarco Emilio BianchiAlessandra AgrestiPublished in: eLife (2016)
Several transcription factors (TFs) oscillate, periodically relocating between the cytoplasm and the nucleus. NF-κB, which plays key roles in inflammation and cancer, displays oscillations whose biological advantage remains unclear. Recent work indicated that NF-κB displays sustained 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-κB behaves as a damped oscillator able to synchronize to a variety of periodic external perturbations with no memory. We imposed synchronous dynamics to prove that transcription of NF-κB-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 chemokine receptor 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 renewing opportunity windows for decision.
Keyphrases
- signaling pathway
- lps induced
- oxidative stress
- working memory
- pi k akt
- gene expression
- nuclear factor
- induced apoptosis
- transcription factor
- cell cycle arrest
- inflammatory response
- toll like receptor
- high frequency
- cell proliferation
- papillary thyroid
- cell death
- young adults
- decision making
- rna seq
- endoplasmic reticulum stress