Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
Biochem Soc Trans. 2022 Dec 16;50(6):1633-1642. doi: 10.1042/BST20220325.
Proper enhancer-promoter interactions are essential to maintaining specific transcriptional patterns and preventing ectopic gene expression. Drosophila is an ideal model organism to study transcriptional regulation due to extensively characterized regulatory regions and the ease of implementing new genetic and molecular techniques for quantitative analysis. The mechanisms of enhancer-promoter interactions have been investigated over a range of length scales. At a DNA level, compositions of both enhancer and promoter sequences affect transcriptional dynamics, including duration, amplitude, and frequency of transcriptional bursting. 3D chromatin topology is also important for proper enhancer-promoter contacts. By working competitively or cooperatively with one another, multiple, simultaneous enhancer-enhancer, enhancer-promoter, and promoter-promoter interactions often occur to maintain appropriate levels of mRNAs. For some long-range enhancer-promoter interactions, extra regulatory elements like insulators and tethering elements are required to promote proper interactions while blocking aberrant ones. This review provides an overview of our current understanding of the mechanism of enhancer-promoter interactions and how perturbations of such interactions affect transcription and subsequent physiological outcomes.
正确的增强子-启动子相互作用对于维持特定的转录模式和防止异位基因表达至关重要。由于具有广泛特征化的调控区域，并且易于实施新的遗传和分子技术进行定量分析，因此果蝇是研究转录调控的理想模式生物。增强子-启动子相互作用的机制已经在一系列长度尺度上进行了研究。在 DNA 水平上，增强子和启动子序列的组成都会影响转录动力学，包括转录爆发的持续时间、幅度和频率。染色质的三维拓扑结构对于增强子-启动子接触也很重要。通过相互竞争或合作，多个同时发生的增强子-增强子、增强子-启动子和启动子-启动子相互作用经常发生，以维持适当的 mRNA 水平。对于一些长距离的增强子-启动子相互作用，需要额外的调节元件，如绝缘子和连接元件，以促进适当的相互作用，同时阻止异常的相互作用。本综述提供了对增强子-启动子相互作用机制的概述，以及这种相互作用的扰动如何影响转录和随后的生理结果。
