Supercoiling-mediated feedback rapidly couples and tunes transcription.
Supercoiling-mediated feedback rapidly couples and tunes transcription.
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DOI：
10.1016/j.celrep.2022.111492
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发表时间：
2022-10-18
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影响因子：
8.8
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转录诱导DNA超螺旋波，改变RNA聚合酶的结合亲和力，重塑基因调控的生化景观。随着超螺旋的迅速扩散，转录动态地重塑了近端基因的调控，形成了一个复杂的反馈回路。然而，需要一个理论框架来整合生物物理调控与生化转录调控。为了研究超螺旋介导的反馈在多基因系统中的作用，我们模拟了超螺旋介导的聚合酶动力学影响下的转录调控，使我们能够识别物理基因间耦合导致的表达模式。我们发现，基因的相对顺序和方向的基因语法定义的表达谱，方差，突发动态，和基因间的相关性的两个基因系统。此外，超螺旋可以增强或减弱生化调节。我们的研究结果表明，超螺旋耦合相邻基因之间的行为，提供了一种调节机制，调谐工程基因网络中的转录变异，并解释了共同定位的天然电路的行为。超卷曲介导的反馈耦合近端基因的转录。在这里，Johnstone和Galloway提供了一个框架，将生化基因调控与DNA超螺旋的生物物理效应相结合。这个统一的模型提供了设计原则，提高基因网络的性能，开发新的监管功能，并访问以前无法访问的监管动态。
Transcription induces a wave of DNA supercoiling, altering the binding affinity of RNA polymerases and reshaping the biochemical landscape of gene regulation. As supercoiling rapidly diffuses, transcription dynamically reshapes the regulation of proximal genes, forming a complex feedback loop. However, a theoretical framework is needed to integrate biophysical regulation with biochemical transcriptional regulation. To investigate the role of supercoiling-mediated feedback within multi-gene systems, we model transcriptional regulation under the influence of supercoiling-mediated polymerase dynamics, allowing us to identify patterns of expression that result from physical inter-gene coupling. We find that gene syntax—the relative ordering and orientation of genes—defines the expression profiles, variance, burst dynamics, and inter-gene correlation of two-gene systems. Furthermore, supercoiling can enhance or weaken biochemical regulation. Our results suggest that supercoiling couples behavior between neighboring genes, providing a regulatory mechanism that tunes transcriptional variance in engineered gene networks and explains the behavior of co-localized native circuits. Supercoiling-mediated feedback couples the transcription of proximal genes. Here, Johnstone and Galloway provide a framework for integrating biochemical gene regulation with the biophysical effects of DNA supercoiling. This unified model provides design principles for improving the performance of gene networks, developing novel regulatory functions, and accessing previously inaccessible regulatory dynamics.