Figure 4. The replication domain model.
Top left, replication timing across three TADs replicated late in cell type 1. Early initiation of flanking regions forms TTRs that extend from the left and right boundaries of TADs 1 and 3 respectively until origins throughout the late-replicating region fire. Top right, TADs 1–3 arrange in transcriptionally repressive compartments of the nucleus. Bottom left, in cell type 2, TAD2 is replicated early, creating new TTRs at pre-existing TAD boundaries. Bottom right, the switch to early replication is associated with diminished interaction with the nuclear lamina and increased interaction with other early-replicating TADs.