1. Computational and Systems Biology
  2. Genomics and Evolutionary Biology
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NF-κB oscillations translate into functionally related patterns of gene expression

  1. Samuel Zambrano
  2. Ilario De Toma
  3. Arianna Piffer
  4. Marco E Bianchi
  5. Alessandra Agresti Is a corresponding author
  1. San Raffaele Scientific Institute, Italy
  2. San Raffaele University, Italy
Research Article
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Cite as: eLife 2016;5:e09100 doi: 10.7554/eLife.09100

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.

Article and author information

Author details

  1. Samuel Zambrano

    1. Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  2. Ilario De Toma

    1. San Raffaele University, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  3. Arianna Piffer

    1. San Raffaele University, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  4. Marco E Bianchi

    1. Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  5. Alessandra Agresti

    1. Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy
    For correspondence
    1. agresti.alessandra@hsr.it
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Suzanne Gaudet, Reviewing Editor, Dana-Farber Cancer Institute, Harvard University, United States

Publication history

  1. Received: June 1, 2015
  2. Accepted: January 13, 2016
  3. Accepted Manuscript published: January 14, 2016 (version 1)
  4. Version of Record published: March 10, 2016 (version 2)

Copyright

© 2016, Zambrano et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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