Histone chaperone Nap1 dismantles an H2A/H2B dimer from a partially unwrapped nucleosome

DNA translocases, such as RNA polymerases, inevitably collide with nucleosomes on eukaryotic chromatin. Upon these collisions, histone chaperones are suggested to facilitate nucleosome disassembly and re-assembly. In this study, by performing in vitro transcription assays and molecular simulations, we found that partial unwrapping of a nucleosome by an RNA polymerase dramatically facilitates an H2A/H2B dimer dismantling from the nucleosome by Nucleosome Assembly Protein 1 (Nap1). Furthermore, the results uncovered molecular mechanisms of Nap1 functions in which the highly acidic C-terminal flexible tails of Nap1 contribute to the H2A/H2B binding by associating with the binding interface buried and not accessible to Nap1 globular domains, supporting the penetrating fuzzy binding mechanism seemingly shared across various histone chaperones. These findings have broad implications for the mechanisms by which histone chaperones process nucleosomes upon collisions with translocases in transcription, histone recycling and nucleosomal DNA repair.

Automated summary

In this study, researchers found that partial unwrapping of a nucleosome by an RNA polymerase significantly facilitates the dismantling of an H2A/H2B dimer from the nucleosome by Nap1. The results also revealed the molecular mechanisms of Nap1 functions, in which the highly acidic C-terminal flexible tails of Nap1 contribute to the binding of H2A/H2B. These findings have important implications for understanding how histone chaperones process nucleosomes upon collisions with translocases.