Relating mammalian replication program to large-scale chromatin folding

Autor: Rasha E. Boulos, Chun-Long Chen, Benjamin Audit, Aurélien Rappailles, Olivier Hyrien, Arach Goldar, Antoine Baker, Hanna Julienne, Guillaume Guilbaud, Claude Thermes, Alain Arneodo, Yves d'Aubenton-Carafa
Rok vydání: 2013
Předmět:
Zdroj: BCB
DOI: 10.1145/2506583.2506699
Popis: We review the existence of a new type of megabase-sized replication domains along the human genome. These domains are revealed in 7 somatic cell types by U-shaped patterns in the replication timing profiles. In the germline, these domains appear as N-shaped patterns in the DNA compositional asymmetry profiles resulting from replication-associated mutational asymmetries. We demonstrated that the average replication fork polarity is directly proportional to both the DNA compositional asymmetry and the derivative of the replication timing profile. Hence, the average fork polarity changes in a linear manner across U/N-replication domains enlightening a robust mode of replication across cell types and during evolution. Using genome-wide chromatin conformation data, we found that the replication domains remarkably coincide with self-interacting folding units of the chromatin fiber and that their borders are long-range interconnected hubs in the chromatin interaction graph. Altogether our results suggest that the spatio-temporal replication program is intimately coupled to a high-order 3D organization of the human genome.
Databáze: OpenAIRE