Transcription factors (TFs) integrate signals to regulate target gene expression, but we generally lack a quantitative understanding of how changes in TF levels regulate mRNA and protein production. Here, we established a system to simultaneously monitor the levels of p53, a TF that shows oscillations following DNA damage, and the transcription and protein levels of its target p21 in individual cells. p21 transcription tracked p53 dynamics, while p21 protein steadily accumulated. p21 transcriptional activation showed bursts of mRNA production, with p53 levels regulating the probability but not magnitude of activation. Variations in p53 levels between cells contributed to heterogeneous p21 transcription while independent p21 alleles exhibited highly correlated behaviors. Pharmacologically elevating p53 increased the probability of p21 transcription with minor effects on its magnitude, leading to a strong increase in p21 protein levels. Our results reveal quantitative mechanisms by which TF dynamics can regulate protein levels of its targets. A record of this paper’s transparent peer review process is included in the Supplemental Information.

转录因子 (TF) 整合信号以调节靶基因表达，但我们通常缺乏对 TF 水平变化如何调节 mRNA 和蛋白质产生的定量理解。在这里，我们建立了一个系统来同时监测 p53 的水平，这是一种在 DNA 损伤后显示振荡的 TF，以及单个细胞中其靶标 p21 的转录和蛋白质水平。p21转录跟踪 p53 动态，而 p21 蛋白稳步积累。p21转录激活显示出 mRNA 产生的爆发，p53 水平调节概率但不调节激活程度。细胞之间 p53 水平的变化有助于异质p21转录，而独立p21等位基因表现出高度相关的行为。药理学升高 p53 增加了p21转录的可能性，但对其幅度影响很小，导致 p21 蛋白水平的强烈增加。我们的结果揭示了 TF 动力学可以调节其目标蛋白质水平的定量机制。本文的透明同行评审过程的记录包含在补充信息中。