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Single-cell replication profiling to measure stochastic variation in mammalian replication timing

Author

Listed:
  • Vishnu Dileep

    (Florida State University)

  • David M. Gilbert

    (Florida State University)

Abstract

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.

Suggested Citation

  • Vishnu Dileep & David M. Gilbert, 2018. "Single-cell replication profiling to measure stochastic variation in mammalian replication timing," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02800-w
    DOI: 10.1038/s41467-017-02800-w
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    Cited by:

    1. Shuangyi Xu & Ning Wang & Michael V. Zuccaro & Jeannine Gerhardt & Rajan Iyyappan & Giovanna Nascimento Scatolin & Zongliang Jiang & Timour Baslan & Amnon Koren & Dieter Egli, 2024. "DNA replication in early mammalian embryos is patterned, predisposing lamina-associated regions to fragility," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Stefano Gnan & Joseph M. Josephides & Xia Wu & Manuela Spagnuolo & Dalila Saulebekova & Mylène Bohec & Marie Dumont & Laura G. Baudrin & Daniele Fachinetti & Sylvain Baulande & Chun-Long Chen, 2022. "Kronos scRT: a uniform framework for single-cell replication timing analysis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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