Project name: Replication-Timing Boundaries Facilitate Cell-type and Species-specific Regulation of a Rearranged Human Chromosome in Mouse

Description: In multicellular organisms, developmental changes to replication timing occur in 400- 800 kb domains across half the genome. While clear examples of epigenetic control of replication timing have been described, a role for DNA sequence in mammalian replication timing has not been substantiated. To assess the role of DNA sequences in directing these changes, 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 demonstrate DNA sequencedriven regulation of Hsa21 replication timing during development and provide evidence that mammalian chromosomes consist of multiple independent units of replication timing regulation.Overall design: Profile comparison of fibroblast and T-cell cultures from trans-chromosomic mice and human and mouse controls.

Data type: Other

Sample scope: Multispecies

Relevance: Other

Release date: 2012-06-05

Last updated: 2012-06-04