Recent advances on mammalian DNA replication initiation and timing: From chromatin features to nuclear organization

In eukaryotes, chromatin state and nuclear architecture are tightly linked to the replication timing (RT) program. Here, we consider how chromatin features operate across all scales of genome organization in mammals, from the local nucleosomal level, with histone variants and their posttranslational modifications, to the global scale that comprises compartments and topologically associated domains (TADs). We discuss recent findings that tie these features with DNA replication; we examine how histone variants and modifications shape replication initiation, how 3D genome architecture may contribute to temporal regulation, and how these local and global scales operate during early mammalian development, when RT emerges de novo. This overview will encourage dissection of principles that establish and maintain RT.