p53 pulses lead to distinct patterns of gene expression albeit similar DNA-binding dynamics.
p53 pulses lead to distinct patterns of gene expression albeit similar DNA-binding dynamics.
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DOI：
10.1038/nsmb.3452
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发表时间：
2017-10
影响因子：
16.8
通讯作者：
Lahav G
中科院分区：
文献类型：
--
作者：
Hafner A;Stewart-Ornstein J;Purvis JE;Forrester WC;Bulyk ML;Lahav G
转录因子的动力学在多种生物系统中起着重要的作用。然而，这些动态被解码成不同转录反应的机制尚不清楚。在这里，我们关注肿瘤抑制蛋白p53的动力学，它在DNA损伤反应中表现出一系列脉冲。我们进行了时间过程RNA-Seq和ChIP-Seq测量，以确定p53脉冲如何与基因表达全基因组相关联。我们发现了多种不同的基因表达模式，以响应p53脉冲。令人惊讶的是，p53结合动力学在所有基因组位点上是一致的，即使是表现出不同mRNA动力学的基因。利用一个数学模型，并辅以对持续p53输入的额外实验测量，我们确定p53与靶基因的结合和激活转录是一致的，而转录后机制是基因表达动态差异的原因。
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-Seq and ChIP-Seq measurements to determine how p53 pulses 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 a sustained p53 input, we determined that p53 binds to and activates transcription of its target genes uniformly, while posttranscriptional mechanisms are responsible for the differences in gene expression dynamics.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
12.4
作者：
通讯作者：
--
影响因子：
64.5
作者：
ELDEIRY, WS;TOKINO, T;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
30.8
作者：
Lahav, G;Rosenfeld, N;Alon, U
通讯作者：
Alon, U
影响因子：
64.8
作者：
Cai, Long;Dalal, Chiraj K.;Elowitz, Michael B.
通讯作者：
Elowitz, Michael B.