美国纪念斯隆-凯特琳癌症中心Alexandros Pertsinidis等科学家在《细胞》发表研究，利用单基因纳米显微技术揭示了远端增强子调控转录的机制。

远端增强子可在巨大的基因组距离上激活基因，但这种通讯如何发生以及传递何种信号仍知之甚少。研究人员利用实时单基因纳米显微技术和靶向扰动，定义了增强子-启动子通讯的物理参数和机制。他们发现，有效相互作用是动态的，发生在约100纳米的邻近距离内，并与转录爆发相协调。增强子和启动子不仅通过被动扩散相互找到；研究人员还经常直接观察到它们被黏连蛋白介导的环挤出主动带到一起，而这是转录爆发频率的关键决定因素。研究人员还发现，RNA聚合酶II机器的特定通用转录因子是启动转录爆发的关键，增强子-启动子相互作用通过将启动子嵌入在增强子处形成的通用转录因子簇中来激活爆发。研究结果解析了参与长距离基因激活的分子和生化信号，并阐明了这些信号从增强子传递至启动子的生物物理机制。

附：英文原文

Title: Mechanisms of transcription control by distal enhancers from single-gene nanoscopy

Author: Lingling Cheng, Chayan De, Jieru Li, Rose Korff, Alexandros Pertsinidis

Issue&Volume: 2026-10-13

Abstract: Distal enhancers activate genes over vast genomic distances, but how this communication occurs and what signals are transmitted are poorly understood. Using real-time single-gene nanoscopy and targeted perturbations, we define physical parameters and mechanisms of enhancer-promoter communication. We find that productive interactions are dynamic, occur at a proximity of 100 nm, and are coordinated with transcriptional bursts. Enhancers and promoters find one another not only through passive diffusion; we often directly observe them being actively brought together by cohesin-mediated loop extrusion, which is a key determinant of transcriptional burst frequency. We also discover that specific general transcription factors (GTFs) of RNA polymerase II machinery are key to initiating transcriptional bursts, and enhancer-promoter interactions activate bursting by embedding the promoter within GTF clusters that form at the enhancers. Our results resolve the molecular and biochemical signals involved in long-range gene activation and elucidate the biophysical mechanisms for their transmission from the enhancer to the promoter.

DOI: 10.1016/j.cell.2026.09.028

Source: https://www.cell.com/cell/abstract/S0092-8674(26)01130-X