Single-cell replication profiling to measure stochastic variation in mammalian replication timing.
Single-cell replication profiling to measure stochastic variation in mammalian replication timing.
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DOI：
10.1038/s41467-017-02800-w
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发表时间：
2018-01-30
影响因子：
16.6
通讯作者：
Gilbert DM
中科院分区：
文献类型：
--
作者：
Dileep V;Gilbert DM
哺乳动物的DNA复制是通过多个复制子片段进行调控的，这些复制子片段在s期以确定的时间顺序进行复制。此外，rd的早期/晚期复制对应于活跃/不活跃的染色质相互作用区室。虽然复制起始点是随机选择的，但对复制时间的变化却知之甚少。在这里，我们设计了一种策略来测量变异的复制时间使用DNA拷贝数在单个小鼠胚胎干细胞。我们发现复制和未复制DNA之间的边界在细胞之间是高度保守的，划分了细胞核的活性和非活性区室。50%的复制事件偏离其S期的平均复制时间±15%。这种变异程度在细胞之间、细胞内的同源物之间以及全基因组范围内的所有结构域之间是相似的，而与它们的复制时间无关。这些结果表明，复制时间的随机变化与决定时间或外部环境变化的因素无关。虽然DNA复制在s期受到暂时调节，但复制时间的变化尚未得到很好的理解。在这里，作者使用单个小鼠ESCs中的DNA拷贝数来测量复制时间的变化，并发现随机变化与调节时间的元素无关。
Mammalian DNA replication is regulated via multi-replicon segments that replicate in a defined temporal order during S-phase. Further, early/late replication of RDs corresponds to active/inactive chromatin interaction compartments. Although replication origins are selected stochastically, variation in replication timing is poorly understood. Here we devise a strategy to measure variation in replication timing using DNA copy number in single mouse embryonic stem cells. We find that borders between replicated and unreplicated DNA are highly conserved between cells, demarcating active and inactive compartments of the nucleus. Fifty percent of replication events deviated from their average replication time by ± 15% of S phase. This degree of variation is similar between cells, between homologs within cells and between all domains genomewide, regardless of their replication timing. These results demonstrate that stochastic variation in replication timing is independent of elements that dictate timing or extrinsic environmental variation. While DNA replication is temporally regulated during S-phase, variation in replication timing is not well understood. Here, the authors measure variation in replication timing using DNA copy number in single mouse ESCs and find stochastic variation to be independent of elements that regulate timing.
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