Work

Roles of histone chaperone Nap1 and histone acetylation in regulating phase-separation of nucleosome arrays

Year: 2025

Type: article

Abstract: Chromatin condensation is dynamically regulated throughout the cell cycle and plays key roles in modulating gene accessibility. The DNA-histone dynamics in the nucleosome are central to the regulation mechanisms of chromatin condensation, which remain poorly understood. Employing fluorescence recovery after photobleaching, optical super-resolution imaging, and microrheology with optical tweezers, we investigated the roles of various parameters in regulating phase-separation of 12-mer nucleosome arrays. Here, we show that histone H4 tail lysine residues are the main drivers of liquid-liquid phase separation of nucleosome arrays. We also show that the condensed liquid-like droplets comprise a mobile fraction and a relatively immobile structural scaffold. Histone chaperone Nap1 and histone H3 tail acetylation enhance DNA-histone dynamics within this scaffold, thereby lowering the overall viscosity of the droplets. These results suggest that histone chaperone and histone H3/H4 tails play critical roles in regulating chromatin condensation and gene accessibility in condensed chromatin.

Source: Nature Communications

DOI: 10.1038/s41467-025-65701-3

Authors: Jia Gao, Hongyun Li, Song Tan, Ruobo Zhou, Tae-Hee Lee

Institution: Pennsylvania State University

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $6,990

Funders: U.S. Department of Health and Human Services, National Institutes of Health, National Institute of General Medical Sciences