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- Title
Replication-timing boundaries facilitate cell-type and species-specific regulation of a rearranged human chromosome in mouse.
- Authors
Pope, Benjamin D; Chandra, Tamir; Buckley, Quinton; Hoare, Matthew; Ryba, Tyrone; Wiseman, Frances K; Kuta, Anna; Wilson, Michael D; Odom, Duncan T; Gilbert, David M
- 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.
- Publication
Human molecular genetics, 2012, Vol 21, Issue 19, p4162
- ISSN
1460-2083
- Publication type
Journal Article
- DOI
10.1093/hmg/dds232