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Single-cell replication profiling to measure stochastic variation in mammalian replication timing
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Single-cell replication profiling to measure stochastic variation in mammalian replication timing
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Single-cell replication profiling to measure stochastic variation in mammalian replication timing
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Journal Article
Single-cell replication profiling to measure stochastic variation in mammalian replication timing
2018
Overview
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.
