{"doi":"10.17615/5v2q-1q30","title":"CCR4/NOT complex associates with the proteasome and regulates histone methylation","abstract":"The proteasome regulates histone lysine methylation and gene transcription, but how it does so is poorly understood. To better understand this process, we used the epistatic miniarray profile (E-MAP) approach to identify factors that genetically interact with proteasomal subunits. In addition to members of the Set1 complex that mediate histone H3 lysine 4 methylation (H3K4me), we found that deleting members of the CCR4/NOT mRNA processing complex exhibit synthetic phenotypes when combined with proteasome mutants. Further biochemical analyses revealed physical associations between CCR4/NOT and the proteasome in vivo. Consistent with the genetic and biochemical interactions linking CCR4/NOT with proteasome and Set1-mediated methylation, we find that loss of Not4 decreases global and gene-specific H3K4 trimethylation (H3K4me3) and decreases 19S proteasome recruitment to the PMA1 gene. Similar to proteasome regulation of histone methylation, loss of CCR4/NOT members does not affect ubiquitinated H2B. Mapping of Not4 identified the RING finger domain as essential for H3K4me3, suggesting a role for ubiquitin in this process. Consistent with this idea, loss of the Not4-interacting protein Ubc4, a known ubiquitin-conjugating enzyme, decreases H3K4me3. These studies implicate CCR4/NOT in the regulation of H3K4me3 through a ubiquitin-dependent pathway that likely involves the proteasome.","journal":"UNC Libraries","year":2020,"id":114863,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":540321,"name":"J. S. Weissman","orcid":null,"position":1,"is_corresponding":false},{"id":440548,"name":"B. D. Strahl","orcid":null,"position":2,"is_corresponding":false},{"id":540322,"name":"P. Kemmeren","orcid":null,"position":3,"is_corresponding":false},{"id":403340,"name":"N. J. Krogan","orcid":null,"position":4,"is_corresponding":false},{"id":540323,"name":"D. P. Mersman","orcid":null,"position":5,"is_corresponding":false},{"id":440546,"name":"Y. Shibata","orcid":null,"position":6,"is_corresponding":false},{"id":527964,"name":"R. N. Laribee","orcid":null,"position":7,"is_corresponding":false},{"id":540324,"name":"S. R. Collins","orcid":null,"position":8,"is_corresponding":false},{"id":540325,"name":"S. D. Briggs","orcid":null,"position":9,"is_corresponding":false},{"id":482775,"name":"Assen Roguev","orcid":"0000-0003-3470-747X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:33.226937Z","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":[]}