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


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.

SUBMITTER: Pope BD 

PROVIDER: S-EPMC3441118 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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

Pope Benjamin D BD   Chandra Tamir T   Buckley Quinton Q   Hoare Matthew M   Ryba Tyrone T   Wiseman Frances K FK   Kuta Anna A   Wilson Michael D MD   Odom Duncan T DT   Gilbert David M DM  

Human molecular genetics 20120626 19


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 tw  ...[more]

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