Replication-timing boundaries facilitate cell-type and species-specific regulation of a rearranged human chromosome in mouse.
Hum Mol Genet
; 21(19): 4162-70, 2012 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-22736031
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 21
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Rearranjo Gênico
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Regulação da Expressão Gênica
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Replicação do DNA
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Camundongos
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article