Open AccessStochastic transcription in the p53‐mediated response to DNA damage is modulated by burst frequency
Author(s) -
Friedrich Dhana,
Friedel Laura,
Finzel Ana,
Herrmann Andreas,
Preibisch Stephan,
Loewer Alexander
Publication year - 2019
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20199068
Subject(s) - biology , dna damage , transcription (linguistics) , dna , computational biology , transcription factor , microbiology and biotechnology , genetics , gene , linguistics , philosophy
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 sm FISH 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.