{"doi":"10.1016/j.celrep.2024.113707","title":"H2A.Z histone variants facilitate HDACi-dependent removal of H3.3K27M mutant protein in pediatric high-grade glioma cells","abstract":"Diffuse intrinsic pontine gliomas (DIPGs) are deadly pediatric brain tumors, non-resectable due to brainstem localization and diffusive growth. Over 80% of DIPGs harbor a mutation in histone 3 (H3.3 or H3.1) resulting in a lysine-to-methionine substitution (H3K27M). Patients with DIPG have a dismal prognosis with no effective therapy. We show that histone deacetylase (HDAC) inhibitors lead to a significant reduction in the H3.3K27M protein (up to 80%) in multiple glioma cell lines. We discover that the SB939-mediated H3.3K27M loss is partially blocked by a lysosomal inhibitor, chloroquine. The H3.3K27M loss is facilitated by co-occurrence of H2A.Z, as evidenced by the knockdown of H2A.Z isoforms. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis confirms the occupancy of H3.3K27M and H2A.Z at the same SB939-inducible genes. We discover a mechanism showing that HDAC inhibition in DIPG leads to pharmacological modulation of the oncogenic H3.3K27M protein levels. These findings show the possibility of directly targeting the H3.3K27M oncohistone.","journal":"Cell Reports","year":2024,"id":433580,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"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":1239847,"name":"Amanda Freitas-Huhtamäki","orcid":null,"position":1,"is_corresponding":false},{"id":1239305,"name":"Chinchu Jayaprakash","orcid":"0000-0001-9967-0095","position":2,"is_corresponding":false},{"id":1239306,"name":"Monika Dźwigońska","orcid":"0000-0003-1774-3671","position":3,"is_corresponding":false},{"id":583513,"name":"Francisca N. de Luna Vitorino","orcid":"0000-0001-8543-2299","position":4,"is_corresponding":false},{"id":269891,"name":"Cynthia Horth","orcid":"0000-0003-2441-6783","position":5,"is_corresponding":false},{"id":1239307,"name":"Kamil Wojnicki","orcid":"0000-0002-1630-4389","position":6,"is_corresponding":false},{"id":1239308,"name":"Bartłomiej Gielniewski","orcid":"0000-0001-8067-0618","position":7,"is_corresponding":false},{"id":1239309,"name":"Paulina Szadkowska","orcid":"0000-0001-8125-4843","position":8,"is_corresponding":false},{"id":324377,"name":"Bożena Kamińska","orcid":"0000-0002-2642-4616","position":9,"is_corresponding":false},{"id":32665,"name":"Javad Nazarian","orcid":"0000-0002-1951-9828","position":10,"is_corresponding":false},{"id":1239310,"name":"Maciej Ciołkowski","orcid":"0000-0003-3919-5792","position":11,"is_corresponding":false},{"id":351789,"name":"Joanna Trubicka","orcid":"0000-0002-9848-3674","position":12,"is_corresponding":false},{"id":351788,"name":"Wiesława Grajkowska","orcid":"0000-0001-8318-5781","position":13,"is_corresponding":false},{"id":74960,"name":"Benjamin A. Garcia","orcid":"0000-0003-3596-4750","position":14,"is_corresponding":false},{"id":70645,"name":"Jacek Majewski","orcid":"0000-0003-3572-9558","position":15,"is_corresponding":false},{"id":1001223,"name":"Jakub Mieczkowski","orcid":"0000-0002-2091-012X","position":17,"is_corresponding":false},{"id":1239304,"name":"Katarzyna B. Leszczyńska","orcid":"0000-0002-3504-1553","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T01:59:49.434790Z","pmid":"38306270","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":[]}