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

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.
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