{"doi":"10.1101/2025.05.09.653121","title":"Roles of histone chaperone Nap1 and histone acetylation in regulating phase-separation of chromatin arrays","abstract":"Chromatin condensation is dynamically regulated throughout the cell cycle and plays key roles in modulating gene accessibility at the highest physical level in a cell. The DNA-histone dynamics in short- and long-range inter-nucleosomal interactions are central to the regulation mechanisms of chromatin condensation which remain under active investigation. We employed 12-mer nucleosome arrays to investigate the roles of histone chaperone Nap1, and histone H3 and H4 N-terminal tails and their acetylation in regulating the formation and the properties of phase-separated chromatin condensates. These arrays form liquid-like condensate droplets under a physiological salt condition of 150 mM NaCl. According to our results from bright-field microscopy, fluorescence recovery after photobleaching, optical super-resolution imaging, and microrheology with optical tweezers, histone H4 tail lysine residues are the main drivers of liquid-liquid phase separation of chromatin arrays. We also found that the condensed liquid-like droplets contain both a mobile fraction and a relatively immobile structural scaffold and that histone chaperone Nap1 and histone H3 tail acetylation facilitate DNA-histone dynamics within the structural scaffold to lower 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":557910,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":864354,"name":"Hongyun Li","orcid":"0000-0003-3332-3132","position":1,"is_corresponding":false},{"id":274210,"name":"Song Tan","orcid":"0000-0002-6698-8475","position":2,"is_corresponding":false},{"id":34315,"name":"Ruobo Zhou","orcid":"0000-0001-8628-0282","position":3,"is_corresponding":false},{"id":44963,"name":"Tae-Hee Lee","orcid":"0000-0003-2034-6394","position":4,"is_corresponding":false},{"id":1086497,"name":"Jia Gao","orcid":"0000-0001-6203-209X","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:55:21.727661Z","pmid":"40463029","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}