Regulation of transcriptional bursting by a naturally oscillating signal.
Regulation of transcriptional bursting by a naturally oscillating signal.
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DOI：
10.1016/j.cub.2013.12.011
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发表时间：
2014-01-20
期刊：
影响因子：
9.2
通讯作者：
Chubb, Jonathan R.
中科院分区：
文献类型：
--
作者：
Corrigan, Adam M.;Chubb, Jonathan R.
转录是高度随机的，以不规则的突发方式发生。为了基因表达的时间和空间精度，细胞必须以某种方式处理这种嘈杂的行为。为了解决如何实现这一点，我们通过直接测量活细胞中的转录和信号动态，研究了自然振荡信号如何引发转录爆发。我们鉴定出盘基网柄菌属基因，该基因表现出与细胞外 cAMP 信号波相同周期的快速转录振荡。爆发接近 cAMP 波的反相，在分化过程中加速转录周期。尽管信号和转录振荡之间的耦合在群体水平上很明显，但单细胞转录爆发保留了相当大的异质性，表明转录不仅仅受信号频率控制。先前的研究表明突发异质性反映了不同的染色质状态。在这里，我们表明异质性是由多种内在和外在线索决定的，并由转录持久性维持。对于持久的转录行为来说不同寻常的是，寿命只有 20 分钟，并且通过对振荡信号的响应，转录状态快速随机化。将转录与快速信号振荡联系起来，可以通过时间平均来减少基因表达异质性，从而提供一种在发育过程中产生精确细胞选择的机制。我们观察活细胞中的耦合信号和转录振荡 振荡总体上是稳健的，但在单细胞水平上是异质的 响应异质性是通过短期转录持久性维持的 振荡可以是控制发育中基因表达噪声的机制 Corrigan 和 Chubb 通过转录爆发的实时成像，观察细胞外信号和下游转录之间的耦合振荡。振荡提供了一种减少转录噪音的机制。
Transcription is highly stochastic, occurring in irregular bursts. For temporal and spatial precision of gene expression, cells must somehow deal with this noisy behavior. To address how this is achieved, we investigated how transcriptional bursting is entrained by a naturally oscillating signal, by direct measurement of transcription together with signal dynamics in living cells. We identify a Dictyostelium gene showing rapid transcriptional oscillations with the same period as extracellular cAMP signaling waves. Bursting approaches antiphase to cAMP waves, with accelerating transcription cycles during differentiation. Although coupling between signal and transcription oscillations was clear at the population level, single-cell transcriptional bursts retained considerable heterogeneity, indicating that transcription is not governed solely by signaling frequency. Previous studies implied that burst heterogeneity reflects distinct chromatin states. Here we show that heterogeneity is determined by multiple intrinsic and extrinsic cues and is maintained by a transcriptional persistence. Unusually for a persistent transcriptional behavior, the lifetime was only 20 min, with rapid randomization of transcriptional state by the response to oscillatory signaling. Linking transcription to rapid signaling oscillations allows reduction of gene expression heterogeneity by temporal averaging, providing a mechanism to generate precision in cell choices during development. We observe coupled signal and transcriptional oscillations in living cells Oscillations are collectively robust but heterogeneous at the single-cell level Response heterogeneity is maintained by a short-term transcriptional persistence Oscillations can be a mechanism to control gene expression noise in development Corrigan and Chubb, through live imaging of transcriptional bursts, observe coupled oscillations between an extracellular signal and downstream transcription. Oscillations provide a mechanism to reduce transcriptional noise.
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发表时间：
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期刊：
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