The ring-shaped cohesin complex topologically entraps two DNA molecules to establish sister chromatid cohesion. Cohesin also shapes the interphase chromatin landscape with wide-ranging implications for gene regulation, and cohesin is thought to achieve this by actively extruding DNA loops without topologically entrapping DNA. The 'loop extrusion' hypothesis finds motivation from in vitro observations-whether this process underlies in vivo chromatin loop formation remains untested. Here, using the budding yeast S. cerevisiae, we generate cohesin variants that have lost their ability to extrude DNA loops but retain their ability to topologically entrap DNA. Analysis of these variants suggests that in vivo chromatin loops form independently of loop extrusion. Instead, we find that transcription promotes loop formation, and acts as an extrinsic motor that expands these loops and defines their ultimate positions. Our results necessitate a re-evaluation of the loop extrusion hypothesis. We propose that cohesin, akin to sister chromatid cohesion establishment at replication forks, forms chromatin loops by DNA-DNA capture at places of transcription, thus unifying cohesin's two roles in chromosome segregation and interphase genome organisation.

中文翻译：

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外源性马达通过内聚蛋白指导染色质环的形成。


环状黏连蛋白复合物拓扑包埋两个 DNA 分子以建立姐妹染色单体内聚。Cohesin 还塑造了间期染色质景观，对基因调控具有广泛的影响，人们认为 cohesin 可以通过主动挤出 DNA 环而不拓扑包埋 DNA 来实现这一目标。“环挤出”假说从体外观察中找到了动力——这个过程是否是体内染色质环形成的基础仍未得到检验。在这里，使用出芽酵母酿酒酵母，我们生成了黏连蛋白变体，这些变体已经失去了挤出 DNA 环的能力，但保留了拓扑捕获 DNA 的能力。对这些变体的分析表明，体内染色质环的形成独立于环挤出。相反，我们发现转录促进了环的形成，并充当扩展这些环并定义其最终位置的外在电机。我们的结果需要重新评估环挤出假说。我们提出，黏连蛋白类似于在复制叉处建立的姐妹染色单体凝聚力，通过在转录位点捕获 DNA-DNA 形成染色质环，从而统一黏连蛋白在染色体分离和间期基因组组织中的两个作用。