Department and School of Medicine, University of California, San Diego, La Jolla, CA, USA.
College of Pharmacy Korea University, 2511 Sejong-ro, Sejong, 30019, Republic of Korea.
Exp Mol Med. 2024 Apr;56(4):772-787. doi: 10.1038/s12276-024-01233-y. Epub 2024 Apr 25.
Although often located at a distance from their target gene promoters, enhancers are the primary genomic determinants of temporal and spatial transcriptional specificity in metazoans. Since the discovery of the first enhancer element in simian virus 40, there has been substantial interest in unraveling the mechanism(s) by which enhancers communicate with their partner promoters to ensure proper gene expression. These research efforts have benefited considerably from the application of increasingly sophisticated sequencing- and imaging-based approaches in conjunction with innovative (epi)genome-editing technologies; however, despite various proposed models, the principles of enhancer-promoter interaction have still not been fully elucidated. In this review, we provide an overview of recent progress in the eukaryotic gene transcription field pertaining to enhancer-promoter specificity. A better understanding of the mechanistic basis of lineage- and context-dependent enhancer-promoter engagement, along with the continued identification of functional enhancers, will provide key insights into the spatiotemporal control of gene expression that can reveal therapeutic opportunities for a range of enhancer-related diseases.
尽管增强子通常位于远离其靶基因启动子的位置，但它们是真核生物时空转录特异性的主要基因组决定因素。自第一个灵长类病毒 40 增强子元件被发现以来，人们一直有兴趣揭示增强子与它们的伙伴启动子相互作用的机制，以确保正确的基因表达。这些研究工作得益于越来越复杂的测序和成像方法的应用，以及创新的（ epi ）基因组编辑技术；然而，尽管提出了各种模型，但增强子-启动子相互作用的原则仍未完全阐明。在这篇综述中，我们概述了真核基因转录领域中与增强子-启动子特异性相关的最新进展。更好地理解谱系和上下文依赖性增强子-启动子结合的机制基础，以及功能性增强子的持续鉴定，将为基因表达的时空控制提供关键见解，从而为一系列与增强子相关的疾病提供治疗机会。
