Journal
CHROMOSOME RESEARCH
Volume 18, Issue 1, Pages 127-136Publisher
SPRINGER
DOI: 10.1007/s10577-009-9100-8
Keywords
Replication Timing; Mammalian Development; Cell Differentiation; Chromosome Domains; Nuclear Organization; Chromatin Structure; Sub-nuclear Positioning; Transcriptional Competence
Funding
- NIH [GM083337]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM083337, P01GM085354] Funding Source: NIH RePORTER
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Studies of replication timing provide a handle into previously impenetrable higher-order levels of chromosome organization and their plasticity during development. Although mechanisms regulating replication timing are not clear, novel genome-wide studies provide a thorough survey of the extent to which replication timing is regulated during most of the early cell fate transitions in mammals, revealing coordinated changes of a defined set of 400-800 kb chromosomal segments that involve at least half the genome. Furthermore, changes in replication time are linked to changes in sub-nuclear organization and domain-wide transcriptional potential, and tissue-specific replication timing profiles are conserved from mouse to human, suggesting that the program has developmental significance. Hence, these studies have provided a solid foundation for linking megabase level chromosome structure to function, and suggest a central role for replication in domain-level genome organization.
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