Department of Biology, New York University, New York, NY 10003, USA.
Development. 2022 Nov 1;149(21). doi: 10.1242/dev.200940.
Transcription in the early Drosophila blastoderm is coordinated by the collective action of hundreds of enhancers. Many genes are controlled by so-called 'shadow enhancers', which provide resilience to environment or genetic insult, allowing the embryo to robustly generate a precise transcriptional pattern. Emerging evidence suggests that many shadow enhancer pairs do not drive identical expression patterns, but the biological significance of this remains unclear. In this study, we characterize the shadow enhancer pair controlling the gene short gastrulation (sog). We removed either the intronic proximal enhancer or the upstream distal enhancer and monitored sog transcriptional kinetics. Notably, each enhancer differs in sog spatial expression, timing of activation and RNA Polymerase II loading rates. In addition, modeling of individual enhancer activities demonstrates that these enhancers integrate activation and repression signals differently. Whereas activation is due to the sum of the two enhancer activities, repression appears to depend on synergistic effects between enhancers. Finally, we examined the downstream signaling consequences resulting from the loss of either enhancer, and found changes in tissue patterning that can be explained by the differences in transcriptional kinetics measured.
在早期果蝇胚胎中，转录是由数百个增强子的集体作用来协调的。许多基因受到所谓的“影子增强子”的控制，这些增强子为环境或遗传损伤提供了弹性，使胚胎能够稳健地生成精确的转录模式。新出现的证据表明，许多影子增强子对并不驱动相同的表达模式，但这一生物学意义仍不清楚。在这项研究中，我们描述了控制基因 short gastrulation（sog）的影子增强子对。我们去除了内含子近端增强子或上游远端增强子，并监测了 sog 的转录动力学。值得注意的是，每个增强子在 sog 的空间表达、激活的时间和 RNA 聚合酶 II 加载率上都有所不同。此外，对单个增强子活性的建模表明，这些增强子以不同的方式整合激活和抑制信号。虽然激活是由两个增强子活性的总和产生的，但抑制似乎取决于增强子之间的协同作用。最后，我们研究了失去任何一个增强子时下游信号转导的后果，并发现了组织模式的变化，这些变化可以用测量到的转录动力学差异来解释。
