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

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Abstract

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 -i.e. 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 3 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.

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Samuel Zambrano

Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy

Competing interests
The authors declare that no competing interests exist.
Ilario De Toma

San Raffaele University, Milan, Italy

Competing interests
The authors declare that no competing interests exist.
Arianna Piffer

San Raffaele University, Milan, Italy

Competing interests
The authors declare that no competing interests exist.
Marco E Bianchi

Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy

Competing interests
The authors declare that no competing interests exist.
Alessandra Agresti

Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy

For correspondence
agresti.alessandra@hsr.it

Competing interests
The authors declare that no competing interests exist.

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