Domain-wide regulation of DNA replication timing during mammalian development.
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.
Pope
Benjamin D
BD
Department of Biological Science, Florida State University, Tallahassee, FL, 32306, USA.
Hiratani
Ichiro
I
Gilbert
David M
DM
D000818:Animals; D004261:DNA Replication; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D006801:Humans; D008322:Mammals / Q000235:genetics*; D051379:Mice; D049951:X Chromosome Inactivation