Department of Molecular and Cellular Biology, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México.
Sci Adv. 2020 Feb 5;6(6):eaax0947. doi: 10.1126/sciadv.aax0947. eCollection 2020 Feb.
The classic picture of flagellum biosynthesis in , inferred from population measurements, depicts a deterministic program where promoters are sequentially up-regulated and are maintained steadily active throughout exponential growth. However, complex regulatory dynamics at the single-cell level can be masked by bulk measurements. Here, we discover that in individual cells, flagellar promoters are stochastically activated in pulses. These pulses are coordinated within specific classes of promoters and comprise "on" and "off" states, each of which can span multiple generations. We demonstrate that in this pulsing program, the regulatory logic of flagellar assembly dictates which promoters skip pulses. Surprisingly, pulses do not require specific transcriptional or translational regulation of the flagellar master regulator, FlhDC, but instead appears to be essentially governed by an autonomous posttranslational circuit. Our results suggest that even topologically simple transcriptional networks can generate unexpectedly rich temporal dynamics and phenotypic heterogeneities.
从群体测量推断， 中鞭毛生物合成的经典图像描绘了一个确定性程序，其中启动子依次上调，并在指数生长过程中保持稳定的活性。然而，单细胞水平的复杂调控动力学可能会被批量测量所掩盖。在这里，我们发现，在单个 细胞中，鞭毛启动子呈脉冲式随机激活。这些脉冲在特定类型的启动子中协调，并包含“开启”和“关闭”状态，每个状态都可以跨越多个世代。我们证明，在这个脉冲程序中，鞭毛组装的调控逻辑决定了哪些启动子跳过脉冲。令人惊讶的是，脉冲不需要对鞭毛主调控因子 FlhDC 进行特定的转录或翻译调控，而是似乎主要由一个自主的翻译后回路控制。我们的结果表明，即使是拓扑结构简单的转录网络也能产生出人意料的丰富的时间动态和表型异质性。
