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Asymmetry between activation and deactivation during a transcriptional pulse

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Dunham, Lee S. S., Momiji, Hiroshi, Harper, Claire V., Downton, Polly J., Hey, Kirsty L., McNamara, Anne, Featherstone, Karen, Spiller, David G., Rand, David A., Finkenstädt, Bärbel, White, Michael R. H. and Davis, Julian R.E. (2017) Asymmetry between activation and deactivation during a transcriptional pulse. Cell Systems, 5 (6). 646-653.E5. doi:10.1016/j.cels.2017.10.013

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Official URL: http://dx.doi.org/10.1016/j.cels.2017.10.013

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Abstract

Transcription in eukaryotic cells occurs in gene-specific bursts or pulses of activity. Recent studies identified a spectrum of transcriptionally active “on-states,” interspersed with periods of inactivity, but these “off-states” and the process of transcriptional deactivation are poorly understood. To examine what occurs during deactivation, we investigate the dynamics of switching between variable rates. We measured live single-cell expression of luciferase reporters from human growth hormone or human prolactin promoters in a pituitary cell line. Subsequently, we applied a statistical variable-rate model of transcription, validated by single-molecule FISH, to estimate switching between transcriptional rates. Under the assumption that transcription can switch to any rate at any time, we found that transcriptional activation occurs predominantly as a single switch, whereas deactivation occurs with graded, stepwise decreases in transcription rate. Experimentally altering cAMP signalling with forskolin or chromatin remodelling with histone deacetylase inhibitor modifies the duration of defined transcriptional states. Our findings reveal transcriptional activation and deactivation as mechanistically independent, asymmetrical processes.

Item Type: Journal Article
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science > Mathematics
Faculty of Science > Statistics
Faculty of Science > Centre for Systems Biology
Library of Congress Subject Headings (LCSH): Eukaryotic cells - Genetics., Genetic transcription., Transcription factors.
Journal or Publication Title: Cell Systems
Publisher: Cell Press
ISSN: 2405-4712
Official Date: 27 December 2017
Dates:
DateEvent
27 December 2017Published
15 November 2017Available
18 October 2017Accepted
Volume: 5
Number: 6
Page Range: 646-653.E5
DOI: 10.1016/j.cels.2017.10.013
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
BB/F01760X/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
091688Wellcome Trusthttp://dx.doi.org/10.13039/100004440
MR/K015885/1[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/M013170/1[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
ASTAA1112.KXH[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
BB/K003097/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
305564Seventh Framework Programmehttp://dx.doi.org/10.13039/100011102

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