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

Hum Mol Genet. 2012 Oct 1;21(19):4162-70. doi: 10.1093/hmg/dds232. Epub 2012 Jun 26.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chromosomes, Human, Pair 21 / genetics*
  • DNA Replication*
  • Female
  • Gene Expression Regulation*
  • Gene Rearrangement*
  • Humans
  • Male
  • Mice / genetics*
  • Mice, Inbred C57BL
  • Species Specificity

Associated data

  • GEO/GSE38472