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引用次数: 0
摘要
增强子是元动物基因表达的主要调控因子,最初在功能上被定义为能以与方向无关和与距离无关的方式激活启动子转录的 DNA 序列。尽管增强子对动物的基因调控至关重要,但人们对增强子对启动子的选择性以及更根本的增强子如何与启动子相互作用并激活转录的机制仍然知之甚少。在这篇综述中,我们首先讨论增强子与启动子在空间和时间上相互作用的现有模型,以及增强子如何影响转录激活。接下来,我们将讨论介导增强子选择性的不同机制,包括抑制、生化相容性和三维基因组结构调控。通过三维聚合物模拟,我们说明了三维基因组折叠机制介导增强子选择性的能力如何因不同的增强子-启动子相互作用机制而强烈不同。最后,我们讨论了最近的技术进步如何为增强子-启动子相互作用机制提供新的见解,以及 Hi-C 和 Micro-C 等方法和成像技术中的技术偏差如何影响其解释。
Enhancer selectivity in space and time: from enhancer–promoter interactions to promoter activation
The primary regulators of metazoan gene expression are enhancers, originally functionally defined as DNA sequences that can activate transcription at promoters in an orientation-independent and distance-independent manner. Despite being crucial for gene regulation in animals, what mechanisms underlie enhancer selectivity for promoters, and more fundamentally, how enhancers interact with promoters and activate transcription, remain poorly understood. In this Review, we first discuss current models of enhancer–promoter interactions in space and time and how enhancers affect transcription activation. Next, we discuss different mechanisms that mediate enhancer selectivity, including repression, biochemical compatibility and regulation of 3D genome structure. Through 3D polymer simulations, we illustrate how the ability of 3D genome folding mechanisms to mediate enhancer selectivity strongly varies for different enhancer–promoter interaction mechanisms. Finally, we discuss how recent technical advances may provide new insights into mechanisms of enhancer–promoter interactions and how technical biases in methods such as Hi-C and Micro-C and imaging techniques may affect their interpretation. Gene regulation in animals depends chiefly on enhancers, yet the underlying mechanisms are poorly understood. This Review discusses enhancer–promoter interactions and transcription activation, focusing on how enhancer–promoter selectivity is achieved and on recent technical advances that may provide new insights into transcription activation.
期刊介绍:
Nature Reviews Molecular Cell Biology is a prestigious journal that aims to be the primary source of reviews and commentaries for the scientific communities it serves. The journal strives to publish articles that are authoritative, accessible, and enriched with easily understandable figures, tables, and other display items. The goal is to provide an unparalleled service to authors, referees, and readers, and the journal works diligently to maximize the usefulness and impact of each article. Nature Reviews Molecular Cell Biology publishes a variety of article types, including Reviews, Perspectives, Comments, and Research Highlights, all of which are relevant to molecular and cell biologists. The journal's broad scope ensures that the articles it publishes reach the widest possible audience.