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

• DOI: 10.1038/s41467-017-02800-w
• Publication Date: 2018-01-24T11:33:27Z
• Authors: Vishnu Dileep; David M. Gilbert
• Keywords: Replication timing; Replicon; Replication; Pre-replication complex; Licensing factor

Mammalian DNA replication is regulated via multi-replicon segments that replicate in a defined temporal order during S-phase. Further, early/late of RDs corresponds to active/inactive chromatin interaction compartments. Although origins are selected stochastically, variation timing poorly understood. Here we devise strategy measure using copy number single mouse embryonic stem cells. We find borders between replicated and unreplicated highly conserved cells, demarcating active inactive compartments the nucleus. Fifty percent events deviated from their average time by ± 15% S phase. This degree similar homologs within cells all domains genomewide, regardless timing. These results demonstrate stochastic independent elements dictate or extrinsic environmental variation.