RT Journal Article
SR Electronic
T1 CTCF-mediated Chromatin Structures Dictate the Spatio-temporal Propagation of Replication Foci
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 525915
DO 10.1101/525915
A1 Qian Peter Su
A1 Ziqing Winston Zhao
A1 Luming Meng
A1 Miao Ding
A1 Weiwei Zhang
A1 Yongzheng Li
A1 Mengzhu Liu
A1 Rongqin Li
A1 Yi-Qin Gao
A1 Xiaoliang Sunney Xie
A1 Yujie Sun
YR 2019
UL http://biorxiv.org/content/early/2019/01/21/525915.abstract
AB Mammalian DNA replication is initiated at numerous replication origins, which are clustered into thousands of replication domains (RDs) across the genome. However, it remains unclear whether the replication origins within each RD are activated stochastically. To understand how replication is regulated at the sub-RD level, we directly visualized the spatio-temporal organization, morphology, and in situ epigenetic signatures of individual replication foci (RFi) across S-phase using super-resolution stochastic optical reconstruction microscopy (STORM). Importantly, we revealed a hierarchical radial pattern of RFi propagation that reverses its directionality from early to late S-phase, and is diminished upon caffeine treatment or CTCF knockdown. Together with simulation and bioinformatic analyses, our findings point to a ‘CTCF-organized REplication Propagation’ (CoREP) model. The CoREP model suggests a non-random selection mechanism for replication activation mediated by CTCF at the sub-RD level, as well as the critical involvement of local chromatin environment in regulating replication in space and time.