In eukaryotes, genomic DNA is packaged into hierarchical higher-order chromatin structures. Regulation of this organization is essential for the faithful maintenance and controlled expression of genetic information. Assembly of the nucleosome─the fundamental unit of chromatin─depends on a tightly coordinated network of histone chaperones that escort histones from their initial synthesis through multiple intermediates to their final deposition into nucleosomes. This review provides an overview of the stepwise journey of histones and the regulatory mechanisms that govern this process. We also highlight major outstanding questions and discuss future directions in the field.
Cho et al. (2026) studied this question.