DNA supercoiling has emerged as a major contributor to gene regulation in bacteria, but how DNA supercoiling impacts transcription dynamics in eukaryotes is unclear. Here, using single-molecule dual-color nascent transcription imaging in budding yeast, we show that transcriptional bursting of divergent and tandem GAL genes is coupled. Temporal coupling of neighboring genes requires rapid release of DNA supercoils by topoisomerases. When DNA supercoils accumulate, transcription of one gene inhibits transcription at its adjacent genes. Transcription inhibition of the GAL genes results from destabilized binding of the transcription factor Gal4. Moreover, wild-type yeast minimizes supercoiling-mediated inhibition by maintaining sufficient levels of topoisomerases. Overall, we discover fundamental differences in transcriptional control by DNA supercoiling between bacteria and yeast and show that rapid supercoiling release in eukaryotes ensures proper gene expression of neighboring genes.

DNA 超螺旋已成为细菌基因调控的主要贡献者，但 DNA 超螺旋如何影响真核生物的转录动力学尚不清楚。在这里，我们在出芽酵母中使用单分子双色新生转录成像，表明不同和串联GAL基因的转录爆发是耦合的。相邻基因的时间耦合需要拓扑异构酶快速释放 DNA 超螺旋。当 DNA 超螺旋积聚时，一个基因的转录会抑制其相邻基因的转录。GAL的转录抑制基因由转录因子 Gal4 的不稳定结合产生。此外，野生型酵母通过维持足够水平的拓扑异构酶最大限度地减少超螺旋介导的抑制作用。总的来说，我们发现细菌和酵母之间通过 DNA 超螺旋进行转录控制的根本差异，并表明真核生物中的快速超螺旋释放确保了邻近基因的正确基因表达。