Brunner Andreas, Morero Natalia RosalÍa, Zhang Wanlu, Hossain M Julius, Lampe Marko, Pflaumer Hannah, Halavatyi Aliaksandr, Peters Jan-Michael, Beckwith Kai S, Ellenberg Jan
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Collaboration for Joint PhD Degree between EMBL and Heidelberg University, Faculty of Biosciences, Heidelberg, Germany.
bioRxiv. 2024 May 30:2024.05.29.596439. doi: 10.1101/2024.05.29.596439.
How cells establish the interphase genome organization after mitosis is incompletely understood. Using quantitative and super-resolution microscopy, we show that the transition from a Condensin to a Cohesin-based genome organization occurs dynamically over two hours. While a significant fraction of Condensins remains chromatin-bound until early G1, Cohesin-STAG1 and its boundary factor CTCF are rapidly imported into daughter nuclei in telophase, immediately bind chromosomes as individual complexes and are sufficient to build the first interphase TAD structures. By contrast, the more abundant Cohesin-STAG2 accumulates on chromosomes only gradually later in G1, is responsible for compaction inside TAD structures and forms paired complexes upon completed nuclear import. Our quantitative time-resolved mapping of mitotic and interphase loop extruders in single cells reveals that the nested loop architecture formed by sequential action of two Condensins in mitosis is seamlessly replaced by a less compact, but conceptually similar hierarchically nested loop architecture driven by sequential action of two Cohesins.
细胞如何在有丝分裂后建立间期基因组组织尚不完全清楚。我们使用定量和超分辨率显微镜表明，从基于凝缩素到基于黏连蛋白的基因组组织的转变在两小时内动态发生。虽然相当一部分凝缩素在G1早期之前仍与染色质结合，但黏连蛋白-STAG1及其边界因子CTCF在末期迅速导入子细胞核，立即作为单个复合物结合染色体，足以构建第一个间期拓扑相关结构域（TAD）结构。相比之下，更丰富的黏连蛋白-STAG2仅在G1后期逐渐在染色体上积累，负责TAD结构内的压缩，并在完成核导入后形成配对复合物。我们对单细胞中有丝分裂和间期环挤压蛋白的定量时间分辨图谱显示，有丝分裂中由两种凝缩素的顺序作用形成的嵌套环结构被由两种黏连蛋白的顺序作用驱动的不太紧凑但概念上相似的分层嵌套环结构无缝取代。
