蒙彼利埃大学Jean-Christophe Andrau团队揭示了G-四联体是控制核小体排斥和RNA聚合酶II暂停的启动子元件。相关论文于2025年7月22日发表于国际顶尖学术期刊《自然—遗传学》杂志上。

在这里，课题组人员发现G-四重体（G4）二级DNA结构在哺乳动物启动子上高度富集。G4s位于启动子核小体排除的最深处，与最大启动子活性相关。小组发现实验G4s在体内和体外排除核小体，而有利于它们的强定位。在模型启动子上，受损的G4s影响转录活性和染色质打开。G4不稳定也导致启动子状态失活，影响向有效RNA生产的过渡。最后，G4的稳定导致近端启动子通路的整体减少。总之，他们的数据引入了G4s作为真正的启动子元件，允许核小体排除并促进RNA聚合酶II的病母释放。

据悉，尽管它们在转录中起着中心作用，但很难定义与真核生物启动子相关的普遍序列。在染色质背景下，转录机制的招募需要启动子打开，但DNA元件如何参与这一过程尚不清楚。

附：英文原文

Title: G-quadruplexes are promoter elements controlling nucleosome exclusion and RNA polymerase II pausing

Author: Esnault, Cyril, Zine El Aabidine, Amal, Robert, Marie-Ccile, Cucchiarini, Anne, Magat, Talha, Pigeot, Alexia, Bouchouika, Soumya, Garcia-Oliver, Encar, Gawron, Kevin, Basyuk, Eugnia, Karpinska, Magdalena A., Kozulic-Pirher, Alja, Luo, Yu, Verga, Daniela, Mourad, Raphael, Radulescu, Ovidiu, Mergny, Jean-Louis, Bertrand, Edouard, Andrau, Jean-Christophe

Issue&Volume: 2025-07-22

Abstract: Despite their central role in transcription, it has been difficult to define universal sequences associated with eukaryotic promoters. Within the chromatin context, recruitment of transcriptional machinery requires promoter opening, but how DNA elements contribute to this process is unclear. Here we show that G-quadruplex (G4) secondary DNA structures are highly enriched at mammalian promoters. G4s are located at the deepest point of nucleosome exclusion at promoters and correlate with maximum promoter activity. We found that experimental G4s exclude nucleosomes in vivo and in vitro while favouring strong positioning. At model promoters, impairing G4s affected both transcriptional activity and chromatin opening. G4 destabilization also resulted in an inactive promoter state and affected the transition to effective RNA production. Finally, G4 stabilization resulted in global reduction of proximal promoter pausing. Altogether, our data introduce G4s as bona fide promoter elements allowing nucleosome exclusion and facilitating pause–release by RNA polymerase II.

DOI: 10.1038/s41588-025-02263-6

Source: https://www.nature.com/articles/s41588-025-02263-6