Fig. 5

“Chromatin Re-organization Induced Selective Initiation” (CRISI) model for selective initiation of DNA replication origins. a In the early G1 phase, the spatial distributions of potential replication origins (gray ribbons) are relatively even in the TAD. The TAD comprises several chromatin loops (blue) organized by CTCF and cohesin at the loop anchors (green rings). PCNA clusters (yellow balls) surrounding the TAD are bound to the nuclear matrix (hazed light blue straws). b, c With transcription proceeding, the chromatin loops undergo structural re-organization along with chromatin domain de-compaction in the G1 phase, exposing a subset of the origins to the periphery of the TAD (pink ribbons). Note that the origin at the sequence boundary of the TAD remains at the TAD periphery in the G1 phase. These peripheral origins are more accessible to the surrounding PCNA clusters and thus become high-efficiency origins for the initiation of DNA replication at the periphery of the TAD. The areas inside the black squares in a and b are shown at higher magnification above