The Histone Chaperones SET/TAF-1 beta and NPM1 Exhibit Conserved Functionality in Nucleosome Remodeling and Histone Eviction in a Cytochrome c-Dependent Manner

Chromatin homeostasis mediates essential processes in eukaryotes, where histone chaperones have emerged as major regulatory factors during DNA replication, repair, and transcription. The dynamic nature of these processes, however, has severely impeded their characterization at the molecular level. Here, fluorescence optical tweezers are applied to follow histone chaperone dynamics in real time. The molecular action of SET/template-activating factor-I beta and nucleophosmin 1-representing the two most common histone chaperone folds-are examined using both nucleosomes and isolated histones. It is shown that these chaperones present binding specificity for fully dismantled nucleosomes and are able to recognize and disrupt non-native histone-DNA interactions. Furthermore, the histone eviction process and its modulation by cytochrome c are scrutinized. This approach shows that despite the different structures of these chaperones, they present conserved modes of action mediating nucleosome remodeling.

Automated summary

This article investigates the crucial role of chromatin homeostasis in eukaryotes, with a focus on the function of histone chaperones in DNA replication, repair, and transcription. The authors use fluorescence optical tweezers to study the dynamics of histone chaperones in real time. They find that SET/template-activating factor-I beta and nucleophosmin 1, representing the two most common histone chaperone folds, exhibit binding specificity for fully dismantled nucleosomes and can disrupt non-native histone-DNA interactions. Additionally, the process of histone eviction and its regulation by cytochrome c are examined. This study reveals conserved mechanisms of action in nucleosome remodeling for these structurally distinct chaperones.