First Author | Pope BD | Year | 2012 |
Journal | Hum Mol Genet | Volume | 21 |
Issue | 19 | Pages | 4162-70 |
PubMed ID | 22736031 | Mgi Jnum | J:187410 |
Mgi Id | MGI:5436369 | Doi | 10.1093/hmg/dds232 |
Citation | Pope BD, et al. (2012) Replication-timing boundaries facilitate cell-type and species-specific regulation of a rearranged human chromosome in mouse. Hum Mol Genet 21(19):4162-70 |
abstractText | 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. |