Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030.
Proc Natl Acad Sci U S A. 2023 Jan 24;120(4):e2216436120. doi: 10.1073/pnas.2216436120. Epub 2023 Jan 19.
Enhancers not only activate target promoters to stimulate messenger RNA (mRNA) synthesis, but they themselves also undergo transcription to produce enhancer RNAs (eRNAs), the significance of which is not well understood. Transcription at the participating enhancer-promoter pair appears coordinated, but it is unclear why and how. Here, we employ cell-free transcription assays using constructs derived from the human locus to demonstrate that transcription at an enhancer and its target promoter is interdependent. This interdependence is observable under conditions where direct enhancer-promoter contact (EPC) takes place. We demonstrate that transcription activation at a participating enhancer-promoter pair is dependent on i) the mutual availability of the enhancer and promoter, ii) the state of transcription at both the enhancer and promoter, iii) local abundance of both eRNA and mRNA, and iv) direct EPC. Our results suggest transcriptional interdependence between the enhancer and the promoter as the basis of their transcriptional concurrence and coordination throughout the genome. We propose a model where transcriptional concurrence, coordination and interdependence are possible if the participating enhancer and promoter are entangled in the form of EPC, reside in a proteinaceous bubble, and utilize shared transcriptional resources and regulatory inputs.
增强子不仅激活靶启动子以刺激信使 RNA（mRNA）合成，而且它们自身也会进行转录以产生增强子 RNA（eRNA），但其意义尚不清楚。参与的增强子-启动子对的转录似乎是协调的，但不清楚原因和方式。在这里，我们使用源自人类 基因座的构建体进行无细胞转录测定，证明了增强子和其靶启动子的转录是相互依赖的。这种相互依赖性在发生直接增强子-启动子接触（EPC）的情况下是可见的。我们证明，参与的增强子-启动子对的转录激活取决于 i）增强子和启动子的相互可用性，ii）增强子和启动子的转录状态，iii）eRNA 和 mRNA 的局部丰度，以及 iv）直接 EPC。我们的结果表明，增强子和启动子之间的转录依赖性是它们在整个基因组中转录一致性和协调性的基础。我们提出了一个模型，如果参与的增强子和启动子以 EPC 的形式纠缠在一起，存在于蛋白质泡中，并利用共享的转录资源和调节输入，则转录一致性、协调性和依赖性是可能的。
