Joseph Henry Laboratories of Physics and the Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Department of Molecular Biology and Howard Hughes Medical Institute, Princeton University, Princeton, NJ 08544, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell. 2018 Oct 18;175(3):835-847.e25. doi: 10.1016/j.cell.2018.09.056.
How transcriptional bursting relates to gene regulation is a central question that has persisted for more than a decade. Here, we measure nascent transcriptional activity in early Drosophila embryos and characterize the variability in absolute activity levels across expression boundaries. We demonstrate that boundary formation follows a common transcription principle: a single control parameter determines the distribution of transcriptional activity, regardless of gene identity, boundary position, or enhancer-promoter architecture. We infer the underlying bursting kinetics and identify the key regulatory parameter as the fraction of time a gene is in a transcriptionally active state. Unexpectedly, both the rate of polymerase initiation and the switching rates are tightly constrained across all expression levels, predicting synchronous patterning outcomes at all positions in the embryo. These results point to a shared simplicity underlying the apparently complex transcriptional processes of early embryonic patterning and indicate a path to general rules in transcriptional regulation.
转录爆发与基因调控的关系是一个持续了十多年的核心问题。在这里,我们测量了早期果蝇胚胎中的新生转录活性,并描述了表达边界处绝对活性水平的可变性。我们证明了边界的形成遵循一个共同的转录原则:单个控制参数决定了转录活性的分布,而与基因身份、边界位置或增强子-启动子结构无关。我们推断出潜在的爆发动力学,并将关键的调节参数确定为基因处于转录活性状态的时间分数。出乎意料的是,聚合酶起始的速率和转换速率在所有表达水平下都受到严格限制,这预测了胚胎中所有位置的同步模式结果。这些结果表明,早期胚胎模式形成的转录过程表面上的复杂性背后存在着共同的简单性,并为转录调控的一般规则指明了方向。