Division of Cell and Developmental Biology, University College London, London, United Kingdom; Laboratory for Molecular Cell Biology, University College London, London, United Kingdom
Edward Tunnacliffe
Division of Cell and Developmental Biology, University College London, London, United Kingdom; Laboratory for Molecular Cell Biology, University College London, London, United Kingdom
Danielle Cannon
Division of Cell and Developmental Biology, University College London, London, United Kingdom; Laboratory for Molecular Cell Biology, University College London, London, United Kingdom
Division of Cell and Developmental Biology, University College London, London, United Kingdom; Laboratory for Molecular Cell Biology, University College London, London, United Kingdom
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 40 s 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.
