Replication-timing boundaries facilitate cell-type and species-specific regulation of a rearranged human chromosome in mouse.
Hum Mol Genet, 2012/10/01;21(19):4162-70.
Pope BD[1], Chandra T, Buckley Q, Hoare M, Ryba T, Wiseman FK, Kuta A, Wilson MD, Odom DT, Gilbert DM
Affiliations
PMID: 22736031DOI: 10.1093/hmg/dds232
Impact factor: 5.121
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.
MeSH terms
Animals; Cell Line; Chromosomes, Human, Pair 21; DNA Replication; Female; Gene Expression Regulation; Gene Rearrangement; Humans; Male; Mice; Mice, Inbred C57BL; Species Specificity
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