{"doi":"10.26508/lsa.202402819","title":"High-resolution analysis of human centromeric chromatin","abstract":"Centromeres are marked by the centromere-specific histone H3 variant CENP-A/CENH3. Throughout the cell cycle, the constitutive centromere-associated network is bound to CENP-A chromatin, but how this protein network modifies CENP-A nucleosome conformations in vivo is unknown. Here, we purify endogenous centromeric chromatin associated with the CENP-C complex across the cell cycle and analyze the structures by single-molecule imaging and biochemical assays. CENP-C complex-bound chromatin was refractory to MNase digestion. The CENP-C complex increased in height throughout the cell cycle culminating in mitosis, and the smaller CENP-C complex corresponds to the dimensions of in vitro reconstituted constitutive centromere-associated network. In addition, we found two distinct CENP-A nucleosomal configurations; the taller variant was associated with the CENP-C complex. Finally, CENP-A mutants partially corrected CENP-C overexpression-induced centromeric transcription and mitotic defects. In all, our data support a working model in which CENP-C is critical in regulating centromere homeostasis by supporting a unique higher order structure of centromeric chromatin and altering the accessibility of the centromeric chromatin fiber for transcriptional machinery.","journal":"Life Science Alliance","year":2025,"id":531850,"datarank":0.2165906397732419,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.00864648560525827,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.00864648560525827,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":3,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9144,"is_data_producer":true,"deposit_databanks":{"PDB":["7QOO"],"GEO":["GSE129351"]},"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":1412626,"name":"Minh Bui","orcid":"0000-0002-7984-3275","position":1,"is_corresponding":false},{"id":999362,"name":"Tatini Rakshit","orcid":"0000-0002-4182-9240","position":2,"is_corresponding":false},{"id":1031093,"name":"Sergei A. Grigoryev","orcid":"0000-0003-1890-1862","position":3,"is_corresponding":false},{"id":45067,"name":"David Sturgill","orcid":"0000-0002-7902-3605","position":4,"is_corresponding":false},{"id":411120,"name":"Yamini Dalal","orcid":"0000-0002-7655-6182","position":5,"is_corresponding":false},{"id":411119,"name":"Daniël P. Melters","orcid":"0000-0003-4809-0562","position":0,"is_corresponding":true}],"reference_count":113,"raw_metadata":null,"created_at":"2026-07-19T02:51:18.928280Z","pmid":"39848706","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":[]}