{"doi":"10.1101/2021.12.17.473155","title":"The MLL3/4 complexes and MiDAC act antagonistically as genome-wide regulators of H4K20ac to control a specific gene expression program","abstract":"Abstract The mitotic deacetylase complex MiDAC has recently been shown to play a vital physiological role in embryonic development and neurite outgrowth. However, how MiDAC functionally intersects with other chromatin-modifying regulators is poorly understood. Here, we describe a physical interaction between the histone H3K27 demethylase UTX, a complex-specific subunit of the enhancer-associated MLL3/4 complexes, and MiDAC. We demonstrate that UTX bridges the association of the MLL3/4 complexes and MiDAC by interacting with ELMSAN1, a scaffolding subunit of MiDAC. Our data shows that MiDAC constitutes a negative genome-wide regulator of H4K20ac, an activity which is counteracted by the MLL3/4 complexes. MiDAC and the MLL3/4 complexes co-localize at many genomic regions, that are enriched for H4K20ac and the enhancer marks H3K4me1, H3K4me2 and H3K27ac. We find that MiDAC antagonizes the recruitment of the MLL3/4 complexes to negatively regulate H4K20ac, H3K4me2 and H3K27ac resulting in transcriptional attenuation of associated genes. In summary, our findings provide a paradigm how the opposing roles of chromatin-modifying components, such as MiDAC and the MLL3/4 complexes, balance the transcriptional output of specific gene expression programs.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":228085,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9602,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":342938,"name":"Wojciech Rosikiewicz","orcid":"0000-0001-7031-3430","position":1,"is_corresponding":false},{"id":473460,"name":"Yurii Sedkov","orcid":"0000-0002-5457-1664","position":2,"is_corresponding":false},{"id":473458,"name":"Baisakhi Mondal","orcid":"0000-0002-8171-4333","position":3,"is_corresponding":false},{"id":473459,"name":"Satish Kallappagoudar","orcid":"0000-0001-9557-176X","position":4,"is_corresponding":false},{"id":832857,"name":"Andrey Tvardovskiy","orcid":"0000-0003-3252-280X","position":5,"is_corresponding":false},{"id":280169,"name":"Richa Bajpai","orcid":null,"position":6,"is_corresponding":false},{"id":267013,"name":"Beisi Xu","orcid":"0000-0003-0099-858X","position":7,"is_corresponding":false},{"id":250571,"name":"Shondra M. Pruett‐Miller","orcid":"0000-0002-3793-585X","position":8,"is_corresponding":false},{"id":84710,"name":"Robert Schneider","orcid":"0000-0001-5303-0973","position":9,"is_corresponding":false},{"id":473465,"name":"Hans‐Martin Herz","orcid":"0000-0003-4780-9176","position":10,"is_corresponding":false},{"id":666063,"name":"Xiaokang Wang","orcid":"0000-0002-9850-9248","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:54:50.414605Z","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":[]}