Replication-timing boundaries facilitate cell-type and species-specific regulation of a rearranged human chromosome in mouse.
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.
Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
Benjamin D
BD
Pope
Tamir
T
Chandra
Quinton
Q
Buckley
Matthew
M
Hoare
Tyrone
T
Ryba
Frances K
FK
Wiseman
Anna
A
Kuta
Michael D
MD
Wilson
Duncan T
DT
Odom
David M
DM
Gilbert
D000818:Animals; D002460:Cell Line; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004261:DNA Replication; D005260:Female; D005786:Gene Expression Regulation; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D051379:Mice / Q000235:genetics*; D008810:Mice, Inbred C57BL; D013045:Species Specificity