The p53 transcription factor confers its potent tumor suppressor functions primarily through the regulation of a large network of target genes. The recent explosion of next generation sequencing protocols has enabled the study of the p53 gene regulatory network (GRN) and underlying mechanisms at an unprecedented depth and scale, helping us to understand precisely how p53 controls gene regulation. Here, we discuss our current understanding of where and how p53 binds to DNA and chromatin, its pioneer-like role, and how this affects gene regulation. We provide an overview of the p53 GRN and the direct and indirect mechanisms through which p53 affects gene regulation. In particular, we focus on delineating the ubiquitous and cell type-specific network of regulatory elements that p53 engages; reviewing our understanding of how, where, and when p53 binds to DNA and the mechanisms through which these events regulate transcription. Finally, we discuss the evolution of the p53 GRN and how recent work has revealed remarkable differences between vertebrates, which are of particular importance to cancer researchers using mouse models.

中文翻译：

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肿瘤抑制因子 p53：从参与 DNA 到靶基因调控。


p53 转录因子主要通过调节大型靶基因网络来赋予其有效的肿瘤抑制功能。最近新一代测序方案的爆炸式增长使得对 p53 基因调控网络 (GRN) 及其潜在机制的研究达到了前所未有的深度和规模，帮助我们准确了解 p53 如何控制基因调控。在这里，我们讨论目前对 p53 与 DNA 和染色质结合的位置和方式的理解、它的先锋作用，以及它如何影响基因调控。我们概述了 p53 GRN 以及 p53 影响基因调控的直接和间接机制。特别是，我们重点描绘 p53 参与的普遍存在的、细胞类型特异性的调控元件网络；回顾我们对 p53 如何、在何处以及何时与 DNA 结合以及这些事件调节转录的机制的理解。最后，我们讨论了 p53 GRN 的进化以及最近的工作如何揭示脊椎动物之间的显着差异，这对于使用小鼠模型的癌症研究人员尤其重要。