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

Benjamin D Pope, Tamir Chandra, Quinton Buckley, Matthew Hoare, Tyrone Ryba, Frances K Wiseman, Anna Kuta, Michael D Wilson, Duncan T Odom, David M Gilbert

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)4162-70
Number of pages9
JournalHuman Molecular Genetics
Volume21
Issue number19
DOIs
Publication statusPublished - 1 Oct 2012

Keywords

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

Fingerprint

Dive into the research topics of 'Replication-timing boundaries facilitate cell-type and species-specific regulation of a rearranged human chromosome in mouse'. Together they form a unique fingerprint.

Cite this