Laboratoire de Biologie Moléculaire Eucaryote, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, 31000 Toulouse, France.
Institut Pasteur, Unité Régulation Spatiale des Génomes, UMR 3525, CNRS, Paris 75015, France.
Mol Cell. 2020 Mar 19;77(6):1279-1293.e4. doi: 10.1016/j.molcel.2020.01.019. Epub 2020 Feb 6.
Cohesin, a member of the SMC complex family, holds sister chromatids together but also shapes chromosomes by promoting the formation of long-range intra-chromatid loops, a process proposed to be mediated by DNA loop extrusion. Here we describe the roles of three cohesin partners, Pds5, Wpl1, and Eco1, in loop formation along either unreplicated or mitotic Saccharomyces cerevisiae chromosomes. Pds5 limits the size of DNA loops via two different pathways: the canonical Wpl1-mediated releasing activity and an Eco1-dependent mechanism. In the absence of Pds5, the main barrier to DNA loop expansion appears to be the centromere. Our data also show that Eco1 acetyl-transferase inhibits the translocase activity that powers loop formation and contributes to the positioning of loops through a mechanism that is distinguishable from its role in cohesion establishment. This study reveals that the mechanisms regulating cohesin-dependent chromatin loops are conserved among eukaryotes while promoting different functions.
黏合蛋白是 SMC 复合物家族的成员，它将姐妹染色单体保持在一起，但也通过促进长距离染色体内环的形成来塑造染色体，这一过程被认为是由 DNA 环挤出介导的。在这里，我们描述了三个黏合蛋白伴侣 Pds5、Wpl1 和 Eco1 在非复制或有丝分裂酿酒酵母染色体上形成环的作用。Pds5 通过两种不同的途径限制 DNA 环的大小：经典的 Wpl1 介导的释放活性和 Eco1 依赖性机制。在没有 Pds5 的情况下，DNA 环扩展的主要障碍似乎是着丝粒。我们的数据还表明，Eco1 乙酰转移酶抑制了环形成的转位酶活性，并通过一种与其在黏合蛋白建立中的作用不同的机制来促进环的定位。这项研究揭示了调节黏合蛋白依赖性染色质环的机制在真核生物中是保守的，同时促进了不同的功能。
