Corrigan, AM;
Tunnacliffe, E;
Cannon, D;
Chubb, JR;
(2016)
A continuum model of transcriptional bursting.
eLife
, 5
, Article e13051. 10.7554/eLife.13051.
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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.
| Type: | Article |
|---|---|
| Title: | A continuum model of transcriptional bursting |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.13051 |
| Publisher version: | http://dx.doi.org/10.1017/jsc.2014.6 |
| Language: | English |
| Additional information: | Copyright © Corrigan et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
| Keywords: | Chromosomes, computational biology, dictyostelium, genes, systems biology |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1477536 |
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