{"doi":"10.1242/jcs.114.19.3529","title":"Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A","abstract":"<jats:p>The mechanisms that specify precisely where mammalian kinetochores form within arrays of centromeric heterochromatin remain largely unknown. Localization of CENP-A exclusively beneath kinetochore plates suggests that this distinctive histone might direct kinetochore formation by altering the structure of heterochromatin within a sub-region of the centromere. To test this hypothesis, we experimentally mistargeted CENP-A to non-centromeric regions of chromatin and determined whether other centromere-kinetochore components were recruited. CENP-A-containing non-centromeric chromatin assembles a subset of centromere-kinetochore components, including CENP-C, hSMC1, and HZwint-1 by a mechanism that requires the unique CENP-A N-terminal tail. The sequence-specific DNA-binding protein CENP-B and the microtubule-associated proteins CENP-E and HZW10 were not recruited, and neocentromeric activity was not detected. Experimental mistargeting of CENP-A to inactive centromeres or to acentric double-minute chromosomes was also not sufficient to assemble complete kinetochore activity. The recruitment of centromere-kinetochore proteins to chromatin appears to be a unique function of CENP-A, as the mistargeting of other components was not sufficient for assembly of the same complex. Our results indicate at least two distinct steps in kinetochore assembly: (1) precise targeting of CENP-A, which is sufficient to assemble components of a centromere-prekinetochore scaffold; and (2) targeting of kinetochore microtubule-associated proteins by an additional mechanism present only at active centromeres.</jats:p>","journal":"Journal of Cell Science","year":2001,"id":598284,"datarank":0.8570599208264055,"base_score":5.713732805509369,"endowment":5.713732805509369,"self_citation_contribution":0.8570599208264055,"citation_network_contribution":0.0,"self_endowment_contribution":0.8570599208264055,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":302,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1532956,"name":"Ilia I. 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The sequence-specific DNA-binding protein CENP-B and the microtubule-associated proteins CENP-E and HZW10 were not recruited, and neocentromeric activity was not detected. Experimental mistargeting of CENP-A to inactive centromeres or to acentric double-minute chromosomes was also not sufficient to assemble complete kinetochore activity. The recruitment of centromere-kinetochore proteins to chromatin appears to be a unique function of CENP-A, as the mistargeting of other components was not sufficient for assembly of the same complex. Our results indicate at least two distinct steps in kinetochore assembly: (1) precise targeting of CENP-A, which is sufficient to assemble components of a centromere-prekinetochore scaffold; and (2) targeting of kinetochore microtubule-associated proteins by an additional mechanism present only at active centromeres.</jats:p>","is_dataset_classified":null,"base_score":5.713732805509369,"endowment":5.713732805509369,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11682612","pmcid":null,"openalex_id":"https://openalex.org/W1957377060","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"CA64255","title":null},{"funder_name":"Wellcome Trust","grant_id":"073915","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA41424","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM59150","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM39068","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM44762","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM48430","title":null}],"total_grants":7,"fwci":5.0293,"citation_percentile":0.96147686,"influential_citations":0,"citation_trend":[{"year":2012,"count":19},{"year":2013,"count":9},{"year":2014,"count":9},{"year":2015,"count":7},{"year":2016,"count":8},{"year":2017,"count":12},{"year":2018,"count":6},{"year":2019,"count":9},{"year":2020,"count":9},{"year":2021,"count":19},{"year":2022,"count":8},{"year":2023,"count":5},{"year":2024,"count":8},{"year":2025,"count":7},{"year":2026,"count":6}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://journals.biologists.com/jcs/article-pdf/114/19/3529/1357214/3529.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1242/jcs.114.19.3529","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/11682612","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.323.2592","host_type":""}],"fields_of_study":["Genomics and Chromatin Dynamics","Chromosomal and Genetic Variations","RNA Research and Splicing"],"mesh_terms":["Centromere Protein A","Amino Acid Sequence","Animals","Autoantigens","Chromatin","Chromosomal Proteins, Non-Histone","DNA-Binding Proteins","Cricetinae","HeLa Cells","Histones","Humans","Microtubule-Associated Proteins","Mitosis","Molecular Sequence Data","Transfection","Gene Expression","CHO Cells","Protein Structure, Tertiary","Kinetochores","Centromere Protein B","Hela Cells"],"keywords":["Centromere","Kinetochore","Biology","Chromatin","Cell biology","Histone","Genetics","Heterochromatin","Nucleosome","Chromosome segregation","Chromosome","DNA","Gene"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T15:25:00.853479Z","pmid":null,"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":[]}