Low Replicative Stress Triggers Cell-Type Specific Inheritable Advanced Replication Timing.

Low Replicative Stress Triggers Cell-Type Specific Inheritable Advanced Replication Timing.
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DOI:
10.3390/ijms22094959
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发表时间:
2021-05-07
影响因子:
5.6
通讯作者:
Bergoglio V
Bergoglio V
中科院分区:
生物学2区
文献类型:
--
作者:
Courtot L;Bournique E;Maric C;Guitton-Sert L;Madrid-Mencía M;Pancaldi V;Cadoret JC;Hoffmann JS;Bergoglio V

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DNA复制时间(RT)反映了起始点激活的时间顺序,是一种稳定、保守的细胞类型特异性过程。在低复制压力下,复制叉的减慢诱导与遗传不稳定性相关的有据可查的RT延迟,但它也可以产生仍然未表征的RT进展。为了表征这些高级起始事件,我们监测了用低剂量阿非迪霉素处理的六个独立的人细胞系的全基因组RT。我们报告说,RT的进步是细胞类型特异性的,涉及大异染色质结构域。重要的是,我们发现一些主要的晚期到早期RT进展可以由无应激的下一代细胞遗传,这是一个独特的过程,与增强的染色质可及性以及子细胞中修改的复制起点景观和基因表达相关。总的来说,这项工作突出了如何低复制压力可能会影响细胞身份的RT进展事件在一个子集的染色体结构域。
DNA replication timing (RT), reflecting the temporal order of origin activation, is known as a robust and conserved cell-type specific process. Upon low replication stress, the slowing of replication forks induces well-documented RT delays associated to genetic instability, but it can also generate RT advances that are still uncharacterized. In order to characterize these advanced initiation events, we monitored the whole genome RT from six independent human cell lines treated with low doses of aphidicolin. We report that RT advances are cell-type-specific and involve large heterochromatin domains. Importantly, we found that some major late to early RT advances can be inherited by the unstressed next-cellular generation, which is a unique process that correlates with enhanced chromatin accessibility, as well as modified replication origin landscape and gene expression in daughter cells. Collectively, this work highlights how low replication stress may impact cellular identity by RT advances events at a subset of chromosomal domains.
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