Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI 53706, USA.
Dev Cell. 2019 Aug 19;50(4):426-435.e4. doi: 10.1016/j.devcel.2019.07.001. Epub 2019 Aug 1.
Transcription is well known to be inherently stochastic and episodic, but the regulation of transcriptional dynamics is not well understood. Here, we analyze how Notch signaling modulates transcriptional bursting during animal development. Our focus is Notch regulation of transcription in germline stem cells of the nematode C. elegans. Using the MS2 system to visualize nascent transcripts and live imaging to record dynamics, we analyze bursting as a function of position within the intact animal. We find that Notch-dependent transcriptional activation is indeed "bursty"; that wild-type Notch modulates burst duration (ON-time) rather than duration of pauses between bursts (OFF-time) or mean burst intensity; and that a mutant Notch receptor, which is compromised for assembly into the Notch transcription factor complex, primarily modifies burst size (duration × intensity). These analyses thus visualize the effect of a canonical signaling pathway on metazoan transcriptional bursting in its native context.
转录过程本质上是随机和阶段性的，但转录动力学的调控还不是很清楚。在这里，我们分析了 Notch 信号如何调节动物发育过程中的转录爆发。我们的重点是 Notch 对秀丽隐杆线虫生殖干细胞中转录的调节。我们使用 MS2 系统来可视化新生转录本，并通过实时成像来记录动态，我们将爆发分析作为完整动物体内位置的函数。我们发现 Notch 依赖性转录激活确实是“爆发性的”；野生型 Notch 调节爆发持续时间（ON 时间），而不是爆发之间的停顿持续时间（OFF 时间）或平均爆发强度；并且一个突变的 Notch 受体，其组装到 Notch 转录因子复合物中受到影响，主要调节爆发大小（持续时间×强度）。因此，这些分析直观地显示了典型信号通路对其天然环境中后生动物转录爆发的影响。
