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Intriguingly, EZH2 automethylation is significantly reduced in diffuse intrinsic pontine glioma (DIPG) cells that carry a lysine-to-methionine substitution in histone H3 (H3K27M), but not in cells that carry either EZH2 or EED mutants that abrogate PRC2 allosteric activation, indicating that H3K27M impairs the intrinsic activity of PRC2. Our study demonstrates a PRC2 self-regulatory mechanism through its EZH1/2-mediated automethylation activity.</jats:p>","journal":"Genes &amp; Development","year":2019,"id":598639,"datarank":0.7230422348407557,"base_score":4.820281565605037,"endowment":4.820281565605037,"self_citation_contribution":0.7230422348407557,"citation_network_contribution":0.0,"self_endowment_contribution":0.7230422348407557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":123,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":14,"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":678954,"name":"Jia-Ray Yu","orcid":"0000-0002-7080-4333","position":1,"is_corresponding":false},{"id":1460936,"name":"Jeffrey Granat","orcid":null,"position":2,"is_corresponding":false},{"id":678955,"name":"Ricardo Saldaña-Meyer","orcid":"0000-0001-8431-2682","position":3,"is_corresponding":false},{"id":674574,"name":"Joshua Andrade","orcid":null,"position":4,"is_corresponding":false},{"id":49844,"name":"Gary LeRoy","orcid":"0000-0002-0769-4944","position":5,"is_corresponding":false},{"id":601985,"name":"Ying Jin","orcid":"0000-0001-9475-7538","position":6,"is_corresponding":false},{"id":1534160,"name":"Peder Lund","orcid":null,"position":7,"is_corresponding":false},{"id":388872,"name":"James M. 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Here, we identify the lysine residues at which EZH1/EZH2 are automethylated with EZH2-K510 and EZH2-K514 being the major such sites in vivo. Automethylated EZH2/PRC2 exhibits a higher level of histone methyltransferase activity and is required for attaining proper cellular levels of H3K27me3. While occurring independently of PRC2 recruitment to chromatin, automethylation promotes PRC2 accessibility to the histone H3 tail. Intriguingly, EZH2 automethylation is significantly reduced in diffuse intrinsic pontine glioma (DIPG) cells that carry a lysine-to-methionine substitution in histone H3 (H3K27M), but not in cells that carry either EZH2 or EED mutants that abrogate PRC2 allosteric activation, indicating that H3K27M impairs the intrinsic activity of PRC2. 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