1/17/2024 0 Comments Define tad![]() Here we localize boundaries of replication domains to the early-replicating border of replication-timing transitions and map their positions in 18 human and 13 mouse cell types. Moreover, attempts to reconcile TADs and LADs to replication-timing data have not revealed a common, underlying domain structure 8, 9, 13. However, TADs can be further sub-stratified into smaller domains, challenging the significance of structures at any particular scale 11, 12. Recent Hi-C mapping has unveiled substructure within chromatin compartments called topologically associating domains (TADs) that are largely conserved in their positions between cell types and are similar in size to replication domains 8, 10. Early and late replication correlate, respectively, with open and closed three-dimensional chromatin compartments identified by high-resolution chromosome conformation capture (Hi-C), and, to a lesser extent, late replication correlates with lamina-associated domains (LADs) 4, 5, 8, 9. In mammals, replication timing is cell-type-specific with at least half the genome switching replication timing during development, primarily in units of 400–800 kilobases (‘replication domains’), whose positions are preserved in different cell types, conserved between species, and appear to confine long-range effects of chromosome rearrangements 2, 3, 4, 5, 6, 7. Eukaryotic chromosomes replicate in a temporal order known as the replication-timing program 1.
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