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Cell cycle dynamics of lamina-associated DNA.
EMBO Reports ( IF 7.7 ) Pub Date : 2020-09-07 , DOI: 10.15252/embr.202050636
Tom van Schaik 1 , Mabel Vos 1 , Daan Peric-Hupkes 1 , Patrick Hn Celie 2 , Bas van Steensel 1, 3
Affiliation  

In mammalian interphase nuclei, more than one thousand large genomic regions are positioned at the nuclear lamina (NL). These lamina‐associated domains (LADs) are involved in gene regulation and may provide a backbone for the folding of interphase chromosomes. Little is known about the dynamics of LADs during interphase, in particular at the onset of G1 phase and during DNA replication. We developed an antibody‐based variant of the DamID technology (named pA‐DamID) that allows us to map and visualize genome–NL interactions with high temporal resolution. Application of pA‐DamID combined with synchronization and cell sorting experiments reveals that LAD–NL contacts are generally rapidly established early in G1 phase. However, LADs on the distal ~25 Mb of most chromosomes tend to contact the NL first and then gradually detach, while centromere‐proximal LADs accumulate gradually at the NL. Furthermore, our data indicate that S‐phase chromatin shows transiently increased lamin interactions. These findings highlight a dynamic choreography of LAD–NL contacts during interphase progression and illustrate the usefulness of pA‐DamID to study the dynamics of genome compartmentalization.

中文翻译:

椎板相关DNA的细胞周期动力学。

在哺乳动物的相间核中,有一千多个大的基因组区域位于核层(NL)处。这些层状相关域(LAD)参与基因调控,并可能为相间染色体折叠提供骨架。关于LAD在相间,特别是在G1期开始和DNA复制期间的动力学知之甚少。我们开发了DamID技术的基于抗体的变体(称为pA‐DamID),该变体使我们能够以高时间分辨率绘制和可视化基因组与NL的相互作用。pA-DamID的应用与同步和细胞分选实验相结合,揭示了LAD-NL接触通常在G1早期迅速建立。但是,大多数染色体〜25 Mb远端的LAD往往先与NL接触,然后逐渐脱离,着丝粒近端LAD在NL逐渐积累。此外,我们的数据表明S相染色质显示出短暂增加的层粘连蛋白相互作用。这些发现突显了LAD–NL接触在相间发展过程中的动态编排,并说明了pA–DamID在研究基因组区室化动力学方面的有用性。
更新日期:2020-11-06
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