该课题组人员设计了多能干细胞，在这种干细胞中，内聚蛋白环外移可以被诱导破坏，而不会混淆细胞周期缺陷。转录失调是细胞类型特异性的，并不是所有具有远端增强子的位点都同样依赖于内聚蛋白外移。使用比较基因组编辑，该课题组证明了超过20万个碱基的增强子-启动子通信可能需要内聚蛋白。
然而，启动子-近端元件可以支持远距离的、不依赖于内聚物的增强作用——即使在强CTCF绝缘体上也是如此。最后，转录动力学和胚胎细胞类型的出现在很大程度上仍然是机械化的，尽管被打乱了。除了建立研究增强子生物学中的内聚蛋白的策略外，他们的工作还提供了对细胞类型和基因组环境特异性的机制见解。
据介绍，增强子是控制启动子转录的关键遗传元件，但它们如何跨大基因组距离传递调控信息仍不清楚。
附：英文原文
Title: Synergy between regulatory elements can render cohesin dispensable for distal enhancer function
Author: Karissa L. Hansen, Annie S. Adachi, Luca Braccioli, Smit Kadvani, Ryan M. Boileau, Moreno Martinovic, Bozhena Pokorny, Rini Shah, Erika C. Anderson, Kaite Zhang, Irié Carel, Kenya Bonitto, Robert Blelloch, Geoffrey Fudenberg, Elzo de Wit, Elphège P. Nora
Issue&Volume: 2025-11-27
Abstract: Enhancers are critical genetic elements controlling transcription from promoters, yet how they convey regulatory information across large genomic distances remains unclear. Here, we engineer pluripotent stem cells in which cohesin loop extrusion can be inducibly disrupted without confounding cell cycle defects. Transcriptional dysregulation is cell type-specific, and not all loci with distal enhancers depend equally on cohesin extrusion. Using comparative genome editing, we demonstrate that enhancer-promoter communication over just 20 kilobases can require cohesin. However, promoter-proximal elements can support long-range, cohesin-independent enhancer action – even across strong CTCF insulators. Finally, transcriptional dynamics and the emergence of embryonic cell types remain largely robust despite disrupted extrusion. Beyond establishing strategies to study cohesin in enhancer biology, our work provides mechanistic insight into cell type- and genomic context-specificity.
DOI: adt4221
Source: https://www.science.org/doi/10.1126/science.adt4221