活细胞中诱导内聚蛋白环挤压轨迹的表征，这一成果由乌得勒支大学Peter H. L. Krijger课题组经过不懈努力而取得。该研究于2025年10月16日发表于国际一流学术期刊《自然—遗传学》杂志上。

为了研究内聚蛋白环外移的详细后果，该课题组开发了靶向内聚蛋白装载器（TArgeted cohesin Loader， TACL），用于控制活细胞中特定基因组位置染色质环形成的泛细胞激活。通过TACL，该课题组人员发现可以存在高度复杂的环状网络，在几乎所有CTCF结合的位点上，具有相互阻断的挤出内聚物复合物，驱动内聚物排队并诱导环锚定。TACL环在STAG2、PDS5A或WAPL急性缺失时延伸。活化的内聚蛋白环外离子阻碍了局部基因的转录，改变了染色质的可及性和H3K27ac的分布。TACL表明加载/萃取离子复合物NIPBL-MAU2可以通过黏附蛋白运输到CTCF位点，但与SMC1一起以不依赖于RAD21的方式运输到增强子。它们能够研究在特定基因组位置激活环的结果。

据悉，内聚蛋白（SMC1-SMC3-RAD21）不断挤出DNA环，将染色体组织到结构域，在特定的DNA结合的CTCF分子上进行路径定位和锚定。

附：英文原文

Title: Characterization of induced cohesin loop extrusion trajectories in living cells

Author: Han, Ruiqi, Huang, Yike, Robers, Michelle J., Magnitov, Mikhail, Vaandrager, Iwan, Allahyar, Amin, Verstegen, Marjon J. A. M., Zhang, Kexin, de Wit, Elzo, de Laat, Wouter, Krijger, Peter H. L.

Issue&Volume: 2025-10-16

Abstract: Cohesin (SMC1–SMC3–RAD21) constantly extrudes DNA loops to organize chromosomes into structural domains, pausing and anchoring at specific DNA-bound CTCF molecules. To study the detailed consequences of cohesin loop extrusion, we developed TArgeted Cohesin Loader (TACL) for controlled pan-cellular activation of chromatin loop formation at defined genomic locations in living cells. With TACL, we show that highly complex looping networks can exist, with extruding cohesin complexes that block each other, drive cohesin queuing and induce loop anchoring at nearly all CTCF-bound sites. TACL loops extend upon acute depletion of STAG2, PDS5A or WAPL. Activated cohesin loop extrusion hinders local gene transcription and can alter chromatin accessibility and H3K27ac distribution. TACL shows that the loading/extrusion complex NIPBL–MAU2 can be transported by cohesin to CTCF sites but, together with SMC1, to enhancers in a RAD21-independent manner. TACL thus enables studying the consequences of activated loop extrusion at defined genomic locations.

DOI: 10.1038/s41588-025-02358-0

Source: https://www.nature.com/articles/s41588-025-02358-0