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Replication-timing boundaries facilitate cell-type and species-specific regulation of a rearranged human chromosome in mouse. | LitMetric

AI Article Synopsis

  • The study investigates how DNA sequences influence the timing of DNA replication in multicellular organisms, specifically within human chromosome 21 rearrangements in mice.
  • Findings show that human-specific replication timing is preserved in mouse cells for Hsa21 sequences, but changes occur near rearrangements, impacting replication timing across regions up to 900 kb.
  • The results suggest that DNA sequences play a crucial role in regulating replication timing during development and indicate that mammalian chromosomes have various segments that independently govern replication timing.

Article Abstract

In multicellular organisms, developmental changes to replication timing occur in 400-800 kb domains across half the genome. While examples of epigenetic control of replication timing have been described, a role for DNA sequence in mammalian replication-timing regulation has not been substantiated. To assess the role of DNA sequences in directing developmental changes to replication timing, we profiled replication timing in mice carrying a genetically rearranged Human Chromosome 21 (Hsa21). In two distinct mouse cell types, Hsa21 sequences maintained human-specific replication timing, except at points of Hsa21 rearrangement. Changes in replication timing at rearrangements extended up to 900 kb and consistently reconciled with the wild-type replication pattern at developmental boundaries of replication-timing domains. Our results are consistent with DNA sequence-driven regulation of Hsa21 replication timing during development and provide evidence that mammalian chromosomes consist of multiple independent units of replication-timing regulation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441118PMC
http://dx.doi.org/10.1093/hmg/dds232DOI Listing

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