Regulation of DNA replication and 3D genome organization during early embryogenesis

Three-dimensional (3D) genome organization underlies virtually all DNA-based transactions. To fully appreciate its functional impact, we must first elucidate how it is established. DNA replication in early embryos offers a unique window into this process, as replication timing (RT) closely mirrors 3D genome architecture, which is absent at fertilization but progressively acquired during development. Here, recent single-cell studies of mouse embryos are synthesized, with a particular focus on how RT emerges during early post-fertilization development. The emerging picture suggests that a somatic-cell-like RT program arises shortly after zygotic genome activation (ZGA). This transition likely unfolds as a series of events, offering a valuable entry point for exploring the biological significance of 3D genome organization and understanding how diverse DNA-based processes are coordinated.