美国加州大学Evgeny Z. Kvon及其研究组的最新研究表明，在哺乳动物发育增强子激活过程中增强子与启动子之间相互作用增加。该项研究成果发表在2024年3月20日出版的《自然-遗传学》上。

研究人员揭示了哺乳动物发育过程中增强子的三维（3D）构象，对十种小鼠胚胎组织中近千个具有体内活动的增强子生成了高分辨率的组织分辨接触图。61%的发育增强子绕过了它们的邻近基因，这些基因通常以启动子CpG甲基化为标志。

大多数增强子显示出组织特异性的三维构象，增强子-启动子和增强子-增强子之间的相互作用在体内增强子激活时会适度且持续地增加。只有不到14%的稳定增强子-启动子相互作用在不同组织间形成；然而，这些稳定的相互作用是在没有增强子的情况下形成的，而且很可能是由邻近CTCF结合所介导。该研究结果凸显了增强子-启动子物理邻近性对哺乳动物发育基因激活的重要性。

据介绍，人们认为远端增强子通过物理接近与其目标启动子相互作用，但仍不清楚这种接近对增强子功能的重要性。

附：英文原文

Title: Increased enhancer–promoter interactions during developmental enhancer activation in mammals

Author: Chen, Zhuoxin, Snetkova, Valentina, Bower, Grace, Jacinto, Sandra, Clock, Benjamin, Dizehchi, Atrin, Barozzi, Iros, Mannion, Brandon J., Alcaina-Caro, Ana, Lopez-Rios, Javier, Dickel, Diane E., Visel, Axel, Pennacchio, Len A., Kvon, Evgeny Z.

Issue&Volume: 2024-03-20

Abstract: Remote enhancers are thought to interact with their target promoters via physical proximity, yet the importance of this proximity for enhancer function remains unclear. Here we investigate the three-dimensional (3D) conformation of enhancers during mammalian development by generating high-resolution tissue-resolved contact maps for nearly a thousand enhancers with characterized in vivo activities in ten murine embryonic tissues. Sixty-one percent of developmental enhancers bypass their neighboring genes, which are often marked by promoter CpG methylation. The majority of enhancers display tissue-specific 3D conformations, and both enhancer–promoter and enhancer–enhancer interactions are moderately but consistently increased upon enhancer activation in vivo. Less than 14% of enhancer–promoter interactions form stably across tissues; however, these invariant interactions form in the absence of the enhancer and are likely mediated by adjacent CTCF binding. Our results highlight the general importance of enhancer–promoter physical proximity for developmental gene activation in mammals.

DOI: 10.1038/s41588-024-01681-2

Source: https://www.nature.com/articles/s41588-024-01681-2