Super-Resolution Imaging Reveals Spatio-Temporal Propagation of Human Replication Foci Mediated by CTCF-Organized Chromatin Structures

Abstract

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 or preferentially near certain chromatin features. To understand how DNA replication in single human cells is regulated at the sub-RD level, we directly visualized and quantitatively characterized the spatio-temporal organization, morphology, and in situ epigenetic signatures of individual replication foci (RFi) across S-phase at super-resolution using stochastic optical reconstruction microscopy (STORM).