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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
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 | ||||||||||||||||||||||||
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| Subjects: | Q Science > QH Natural history > QH426 Genetics | ||||||||||||||||||||||||
| Divisions: | Faculty of Science > Mathematics Faculty of Science > Statistics Faculty of Science > Centre for Systems Biology |
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| 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: |
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| Date of first compliant deposit: | 7 December 2017 | ||||||||||||||||||||||||
| 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: |
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