Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
The Center for Genome Architecture, Baylor College of Medicine, Houston, United States.
Elife. 2020 Feb 17;9:e52091. doi: 10.7554/eLife.52091.
Eukaryotic genomes are folded into loops. It is thought that these are formed by cohesin complexes extrusion, either until loop expansion is arrested by CTCF or until cohesin is removed from DNA by WAPL. Although WAPL limits cohesin's chromatin residence time to minutes, it has been reported that some loops exist for hours. How these loops can persist is unknown. We show that during G1-phase, mammalian cells contain acetylated cohesin which binds chromatin for hours, whereas cohesin binds chromatin for minutes. Our results indicate that CTCF and the acetyltransferase ESCO1 protect a subset of cohesin complexes from WAPL, thereby enable formation of long and presumably long-lived loops, and that ESCO1, like CTCF, contributes to boundary formation in chromatin looping. Our data are consistent with a model of nested loop extrusion, in which acetylated cohesin forms stable loops between CTCF sites, demarcating the boundaries of more transient cohesin extrusion activity.
真核基因组折叠成环。人们认为这些环是由黏合蛋白复合物挤出形成的，要么直到环的扩张被 CTCF 阻止，要么直到 WAPL 将黏合蛋白从 DNA 上移除。尽管 WAPL 将黏合蛋白在染色质上的停留时间限制在几分钟内，但据报道，有些环存在数小时。这些环如何能够持续存在尚不清楚。我们表明，在 G1 期，哺乳动物细胞含有乙酰化的黏合蛋白，其可结合染色质数小时，而黏合蛋白结合染色质的时间为几分钟。我们的结果表明，CTCF 和乙酰转移酶 ESCO1 保护黏合蛋白复合物的一部分免受 WAPL 的影响，从而能够形成长的、可能是长寿的环，并且 ESCO1 像 CTCF 一样，有助于染色质环化中的边界形成。我们的数据与嵌套环挤出模型一致，其中乙酰化的黏合蛋白在 CTCF 位点之间形成稳定的环，标记更短暂的黏合蛋白挤出活性的边界。
