Abstract

Transcription occurs in stochastic bursts. Early models based upon RNA hybridisation studies suggest bursting dynamics arise from alternating inactive and permissive states. Here we investigate bursting mechanism in live cells by quantitative imaging of actin gene transcription, combined with molecular genetics, stochastic simulation and probabilistic modelling. In contrast to early models, our data indicate a continuum of transcriptional states, with a slowly fluctuating initiation rate converting the gene between different levels of activity, interspersed with extended periods of inactivity. We place an upper limit of 40s on the lifetime of fluctuations in elongation rate, with initiation rate variations persisting an order of magnitude longer. TATA mutations reduce the accessibility of high activity states, leaving the lifetime of on- and off-states unchanged. A continuum or spectrum of gene states potentially enables a wide dynamic range for cell responses to stimuli.

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  1. Adam M Corrigan

    Laboratory for Molecular Cell Biology, Division of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Edward Tunnacliffe

    Laboratory for Molecular Cell Biology, Division of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Danielle Cannon

    Laboratory for Molecular Cell Biology, Division of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Jonathan R Chubb

    Laboratory for Molecular Cell Biology, Division of Cell and Developmental Biology, University College London, London, United Kingdom
    For correspondence
    j.chubb@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2016, Corrigan 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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  1. Adam M Corrigan
  2. Edward Tunnacliffe
  3. Danielle Cannon
  4. Jonathan R Chubb
(2016)
A continuum model of transcriptional bursting
eLife 5:e13051.
https://doi.org/10.7554/eLife.13051

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https://doi.org/10.7554/eLife.13051