부산대학교 도서관

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. Synopsis: Time‐resolved gene expression measurements show that p53 induction leads to increased burst frequencies at target promoters. The promoters can be grouped into "sustained", "pulsatile" and "transient", and these patterns are sensitive to p53 dynamics and C‐terminal acetylation state. Pulsatile p53 dynamics upon DNA damage lead to an increase in the number of actively transcribing target gene promoters.The transcriptional activity of p53 targets is regulated in a gene‐specific manner and changes between the first and second p53 pulse leading to distinct expression patterns over time.Perturbations of p53 dynamics using small molecule inhibitors after the first accumulation pulse highlight that the C‐terminal acetylation state of p53 contributes to a gene‐specific regulation of TSS activity. [ABSTRACT FROM AUTHOR]