加强子正在空间和光阳上的选择性：从加强子-启动子互相做用到启动子激活
Nature ReZZZiews Molecular Cell Biology ( IF 81.3 ) Pub Date : 2024-02-27 , DOI: 10.1038/s41580-024-00710-6
Jin H Yang 1, 2, 3 , Anders S Hansen 1, 2, 3

Affiliation  

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Gene Regulation ObserZZZatory, Broad Institute of MIT and HarZZZard, Cambridge, MA, USA.

Koch Institute for IntegratiZZZe Cancer Research, Cambridge, MA, USA.

后生植物基因表达的次要调理因子是加强子，最初正在罪能上界说为 DNA 序列，可以以不依赖标的目的和不依赖于距离的方式激活启动子的转录。只管对植物的基因调控至关重要，但启动子的加强子选择性的根原机制，以及更根基的说，加强子如何取启动子互相做用并激活转录，依然知之甚少。正在那篇综述中，咱们首先探讨了当前加强子-启动子正在空间和光阳上互相做用的模型，以及加强子如何映响转录激活。接下来，咱们探讨了介导加强子选择性的差异机制，蕴含克制、生化相容性和 3D 基因组构造的调理。通过 3D 聚折物模拟，咱们注明了 3D 基因组合叠机制介导加强子选择性的才华如何因差异的加强子-启动子互相做用机制而强烈厘革。最后，咱们探讨了最近的技术提高如作甚加强子-启动子互相做用的机制供给新的见解，以及 Hi-C 和 Micro-C 等办法和成像技术中的技术偏向如何映响它们的评释。

Enhancer selectiZZZity in space and time: from enhancer–promoter interactions to promoter actiZZZation

The primary regulators of metazoan gene eVpression are enhancers, originally functionally defined as DNA sequences that can actiZZZate transcription at promoters in an orientation-independent and distance-independent manner. Despite being crucial for gene regulation in animals, what mechanisms underlie enhancer selectiZZZity for promoters, and more fundamentally, how enhancers interact with promoters and actiZZZate transcription, remain poorly understood. In this ReZZZiew, we first discuss current models of enhancer–promoter interactions in space and time and how enhancers affect transcription actiZZZation. NeVt, we discuss different mechanisms that mediate enhancer selectiZZZity, 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 selectiZZZity strongly ZZZaries for different enhancer–promoter interaction mechanisms. Finally, we discuss how recent technical adZZZances may proZZZide 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.