Biological relevance of ConsTADs. (A) Relative profiles of several biological features within ConsTADs and adjacent regions in GM12878. (B) Five clusters of topological domains with distinct DNA replication signals accompanied by the variances of the Repli-seq signal, the average RNA-seq signal, and the boundary type components within each type of domains. (C) Hi-C contact maps of a region on Chromosome 2 of GM12878 accompanied by the ConsTADs (black frames in contact map), the corresponding boundary types and domain types, and ChIP-seq and Repli-seq profiles. (D) Five clusters of topological domains with distinct relative DNA replication models, which indicate the relative early or late replication timing of chromatin regions within each domain. (E) Mean profiles of the relative DNA replication signals for five clusters of domains in D. Arrows indicate the direction of DNA replication from early to late. (F) Average number of CTCF binding peaks around the upstream and downstream boundary for each domain in five clusters. Mann–Whitney U tests were performed to get the P-values. (G) The replication domain model. (Left) DNA replication timing across TADs belonging to early, transition, and late replication domains accompanied with the CTCF profiles at TAD boundaries. (Right) The corresponding chromatin arrangement of replication domains and their chromatin states and prominent modifications.
