Enhancer Priming Enables Fast and Sustained Transcriptional Responses to Notch Signaling
Enhancer Priming Enables Fast and Sustained Transcriptional Responses to Notch Signaling
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DOI：
10.1016/j.devcel.2019.07.002
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发表时间：
2019-08-19
影响因子：
11.8
通讯作者：
Bray, Sarah J.
中科院分区：
文献类型：
--
作者：
Falo-Sanjuan, Julia;Lammers, Nicholas C.;Bray, Sarah J.
来自发育信号通路的信息必须被准确解码以产生转录结果。在Notch的情况下，胞内结构域（NICD）将信号直接转导至细胞核。增强子如何在发育决定的真实的时间内破译NICD尚不清楚。使用MS 2-MCP系统可视化果蝇胚胎单细胞中的新生转录本，我们揭示了两个目标增强子如何读取Notch活性以产生同步和持续的转录谱。通过操纵NICD的水平和改变增强子内的特定基序，我们揭示了两个关键原则。首先，增加NICD水平通过增加转录爆发的持续时间而不是频率来改变转录。其次，NICD需要组织特异性转录因子引发增强子以赋予同步和持续的活性;在它们不存在的情况下，转录是随机和突发的。因此，单个增强子对NICD的动态响应取决于细胞环境而不同。
Information from developmental signaling pathways must be accurately decoded to generate transcriptional outcomes. In the case of Notch, the intracellular domain (NICD) transduces the signal directly to the nucleus. How enhancers decipher NICD in the real time of developmental decisions is not known. Using the MS2-MCP system to visualize nascent transcripts in single cells in Drosophila embryos, we reveal how two target enhancers read Notch activity to produce synchronized and sustained profiles of transcription. By manipulating the levels of NICD and altering specific motifs within the enhancers, we uncover two key principles. First, increased NICD levels alter transcription by increasing duration rather than frequency of transcriptional bursts. Second, priming of enhancers by tissue-specific transcription factors is required for NICD to confer synchronized and sustained activity; in their absence, transcription is stochastic and bursty. The dynamic response of an individual enhancer to NICD thus differs depending on the cellular context.