Abstract
From their molecular birth until their incorporation into chromatin, histones are bound by specific chaperones that serve unique functions in histone trafficking, stability, and chromatin deposition. The H3-specific chaperone NASP binds directly to H3 and is required to prevent degradation of soluble H3 in vivo. Where NASP functions and how NASP affects H3 dynamics and stability are unknown. Using the Drosophila early embryo as a model system to understand NASP function in vivo, we show that NASP does not directly affect H3 nuclear import or export rates. Rather, reduced H3 levels in NASP-deficient embryos indirectly affect nuclear import and the amount of H3 deposited into chromatin. Crucially, we find that cytoplasmic NASP prevents H3 aggregation in vivo and that H3 aggregation and degradation are developmentally separable events. Thus, we propose the main function of NASP in vivo is to prevent H3 aggregation, thereby indirectly protecting H3 from degradation.
