PT  - JOURNAL ARTICLE
AU  - Katherine A. Giles
AU  - Noa Lamm
AU  - Phillippa C. Taberlay
AU  - Anthony J. Cesare
TI  - Three-dimensional chromatin organisation shapes origin activation and replication fork directionality
AID  - 10.1101/2022.06.24.497492
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.24.497492
4099  - http://biorxiv.org/content/early/2022/06/24/2022.06.24.497492.short
4100  - http://biorxiv.org/content/early/2022/06/24/2022.06.24.497492.full
AB  - Faithful DNA replication requires the orderly firing of replication origins across the genome. At present, we lack details around how origins are selected for activation and the subsequent impact of this on replication dynamics. Here, we have investigated how chromatin organisation contributes to replication initiation and dynamics by intersecting ChIP-seq, Hi-C, Repli-seq, and OK-seq data from primary and tumour cells lines. We found replication initiation is significantly enriched at TAD boundaries, co-localizing with CTCF and cohesin in early and mid S-phase. Strong replication fork directionality (RFD) from initiation zones in TAD boundaries could occur in a bi- or uni-directional manner, which highly correlated with replication timing. While TAD boundaries were largely invariant, a minority of initiation zones were shared across cell lines, indicative of cell type specific regulation. These data are consistent with chromatin structure organizing replication initiation and dynamics, ensuring orderly completion of replication from TAD boundaries into TAD internal regions.Competing Interest StatementThe authors have declared no competing interest.