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Stochastic transcription in the p53‐mediated response to DNA damage is modulated by burst frequency

Friedrich, Dhana and Friedel, Laura and Finzel, Ana and Herrmann, Andreas and Preibisch, Stephan and Loewer, Alexander (2019):
Stochastic transcription in the p53‐mediated response to DNA damage is modulated by burst frequency.
In: Molecular Systems Biology, 15, (12), EMBOpress, e-ISSN 1744-4292,
DOI: 10.25534/tuprints-00011601,
[Online-Edition: https://doi.org/10.15252/msb.20199068],
Secondary publishing via DEAL-contract with Wiley, [Article]

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Item Type: Article
Origin: Secondary publishing via DEAL-contract with Wiley
Title: Stochastic transcription in the p53‐mediated response to DNA damage is modulated by burst frequency
Language: English
Abstract:

Discontinuous transcription has been described for different mammalian cell lines and numerous promoters. However, our knowledge of how the activity of individual promoters is adjusted by dynamic signaling inputs from transcription factors is limited. To address this question, we characterized the activity of selected target genes that are regulated by pulsatile accumulation of the tumor suppressor p53 in response to ionizing radiation. We performed time-resolved measurements of gene expression at the single-cell level by smFISH and used the resulting data to inform a mathematical model of promoter activity. We found that p53 target promoters are regulated by frequency modulation of stochastic bursting and can be grouped along three archetypes of gene expression. The occurrence of these archetypes cannot solely be explained by nuclear p53 abundance or promoter binding of total p53. Instead, we provide evidence that the time-varying acetylation state of p53’s C-terminal lysine residues is critical for gene-specific regulation of stochastic bursting.

Journal or Publication Title: Molecular Systems Biology
Journal volume: 15
Number: 12
Publisher: EMBOpress
Classification DDC: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Divisions: 10 Department of Biology > Systems Biology of the Stress Response
Date Deposited: 31 Mar 2020 08:19
Last Modified: 31 Mar 2020 08:19
DOI: 10.25534/tuprints-00011601
Official URL: https://doi.org/10.15252/msb.20199068
URN: urn:nbn:de:tuda-tuprints-116015
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/11601
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