The dynamics of transcription factors play important roles in a variety of biological systems. However, the mechanisms by which these dynamics are decoded into different transcriptional responses are not well understood. Here we focus on the dynamics of the tumor-suppressor protein p53, which exhibits a series of pulses in response to DNA damage. We performed time course RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) measurements to determine how p53 oscillations are linked with gene expression genome wide. We discovered multiple distinct patterns of gene expression in response to p53 pulses. Surprisingly, p53-binding dynamics were uniform across all genomic loci, even for genes that exhibited distinct mRNA dynamics. Using a mathematical model, supported by additional experimental measurements in response to sustained p53 input, we determined that p53 binds to and activates transcription of its target genes uniformly, whereas post-transcriptional mechanisms are responsible for the differences in gene expression dynamics.

中文翻译：

---

p53脉冲导致基因表达的不同模式，尽管DNA结合动力学相似

转录因子的动力学在各种生物系统中起重要作用。但是，这些动力学被解码为不同的转录反应的机制还没有被很好地理解。在这里，我们关注于肿瘤抑制蛋白p53的动力学，该蛋白表现出一系列响应DNA损伤的脉冲。我们进行了时程RNA测序（RNA-seq）和染色质免疫沉淀测序（ChIP-seq）测量，以确定p53振荡如何与全基因表达基因组联系起来。我们发现了响应p53脉冲的基因表达的多种不同模式。出乎意料的是，p53结合动力学在所有基因组位点上都是一致的，即使对于表现出明显的mRNA动力学的基因也是如此。使用数学模型，