{"doi":"10.1016/j.molcel.2024.08.025","title":"Activation of automethylated PRC2 by dimerization on chromatin","abstract":"Polycomb repressive complex 2 (PRC2) is an epigenetic regulator that trimethylates lysine 27 of histone 3 (H3K27me3) and is essential for embryonic development and cellular differentiation. H3K27me3 is associated with transcriptionally repressed chromatin and is established when PRC2 is allosterically activated upon methyl-lysine binding by the regulatory subunit EED. Automethylation of the catalytic subunit enhancer of zeste homolog 2 (EZH2) stimulates its activity by an unknown mechanism. Here, we show that human PRC2 forms a dimer on chromatin in which an inactive, automethylated PRC2 protomer is the allosteric activator of a second PRC2 that is poised to methylate H3 of a substrate nucleosome. Functional assays support our model of allosteric trans -autoactivation via EED, suggesting a previously unknown mechanism mediating context-dependent activation of PRC2. Our work showcases the molecular mechanism of auto-modification-coupled dimerization in the regulation of chromatin-modifying complexes.","journal":"Molecular Cell","year":2024,"id":441152,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1170079,"name":"Egor Pavlenko","orcid":"0000-0003-0293-052X","position":1,"is_corresponding":false},{"id":1170080,"name":"Trinity Cookis","orcid":"0000-0002-5145-7508","position":2,"is_corresponding":false},{"id":1170081,"name":"Linda C. Zirden","orcid":"0000-0003-2635-757X","position":3,"is_corresponding":false},{"id":1170518,"name":"Juliane Renn","orcid":null,"position":4,"is_corresponding":false},{"id":1170082,"name":"Ankush Singhal","orcid":"0000-0003-2949-6962","position":5,"is_corresponding":false},{"id":1170083,"name":"Pascal Hunold","orcid":"0000-0002-7087-5908","position":6,"is_corresponding":false},{"id":1254218,"name":"Michaela Nicole Hoehne‐Wiechmann","orcid":null,"position":7,"is_corresponding":false},{"id":1170085,"name":"Olivia van Ray","orcid":"0000-0002-1449-0018","position":8,"is_corresponding":false},{"id":75676,"name":"Farnusch Kaschani","orcid":"0000-0001-6572-3232","position":9,"is_corresponding":false},{"id":75678,"name":"Markus Kaiser","orcid":"0000-0002-6540-8520","position":10,"is_corresponding":false},{"id":1170086,"name":"Robert Hänsel‐Hertsch","orcid":"0000-0002-2835-4471","position":11,"is_corresponding":false},{"id":301767,"name":"Karissa Y. Sanbonmatsu","orcid":"0000-0002-7965-7392","position":12,"is_corresponding":false},{"id":308992,"name":"Eva Nogales","orcid":"0000-0001-9816-3681","position":13,"is_corresponding":false},{"id":1046627,"name":"Simon Poepsel","orcid":"0000-0002-8304-4062","position":14,"is_corresponding":false},{"id":806989,"name":"Paul Sauer","orcid":"0000-0001-7204-5863","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T02:01:06.281460Z","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":[]}