Molecular mechanism of H2A/H2B dismantling from a partially unwrapped nucleosome by Nap1.

Abstract

During DNA transactions on chromatin such as transcription, replication, and DNA repair, RNA polymerases, replicative helicases, exonucleases, and so on inevitably collide with nucleosomes and unwrap nucleosomal DNA. Histones, components of a nucleosome, contain epigenetic information in the form of chemical modification, which regulates cell growth and fates. To maintain such information upon unwrapping, nucleosomes ahead of the DNA translocases are supposed to be temporarily disassembled. Histone chaperones are proteins modulating histone binding to DNA. However, the roles of histone chaperones in the nucleosome processing upon unwrapping remain unclear. In this study, we performed in vitro transcription assays and coarse-grained molecular dynamics simulations, showing that a histone chaperone, Nap1, dismantles H2A/H2B from a partially unwrapped nucleosome. Moreover, the simulation results reveal that highly acidic C-terminal tails of Nap1 bind to the exposed H2A/H2B via its binding interface not accessible to the Nap1 globular domain, leading to the H2A/H2B dismantling. These findings provide implications for the molecular mechanism by which histone chaperones process nucleosomes during DNA transactions on chromatin.