{"doi":"10.1016/j.molcel.2023.03.013","title":"Structural and functional properties of mSWI/SNF chromatin remodeling complexes revealed through single-cell perturbation screens","abstract":"The mammalian SWI/SNF (mSWI/SNF or BAF) family of chromatin remodeling complexes play critical roles in regulating DNA accessibility and gene expression. The three final-form subcomplexes-cBAF, PBAF, and ncBAF-are distinct in biochemical componentry, chromatin targeting, and roles in disease; however, the contributions of their constituent subunits to gene expression remain incompletely defined. Here, we performed Perturb-seq-based CRISPR-Cas9 knockout screens targeting mSWI/SNF subunits individually and in select combinations, followed by single-cell RNA-seq and SHARE-seq. We uncovered complex-, module-, and subunit-specific contributions to distinct regulatory networks and defined paralog subunit relationships and shifted subcomplex functions upon perturbations. Synergistic, intra-complex genetic interactions between subunits reveal functional redundancy and modularity. Importantly, single-cell subunit perturbation signatures mapped across bulk primary human tumor expression profiles both mirror and predict cBAF loss-of-function status in cancer. Our findings highlight the utility of Perturb-seq to dissect disease-relevant gene regulatory impacts of heterogeneous, multi-component master regulatory complexes.","journal":"Molecular Cell","year":2023,"id":2053,"datarank":0.5495342469194471,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"self_citation_contribution":0.5495342469194471,"citation_network_contribution":0.0,"self_endowment_contribution":0.5495342469194471,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0514,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-04-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":23984,"name":"Oana Ursu","orcid":"0000-0001-8743-4730","position":1,"is_corresponding":false},{"id":23985,"name":"Alexander P. Wu","orcid":"0009-0009-4059-3019","position":2,"is_corresponding":false},{"id":23986,"name":"Evan B. Winter","orcid":null,"position":3,"is_corresponding":false},{"id":3743,"name":"Michael S. Cuoco","orcid":"0000-0003-2163-5120","position":4,"is_corresponding":false},{"id":3622,"name":"Sai Ma","orcid":"0000-0002-9785-7929","position":5,"is_corresponding":false},{"id":23987,"name":"Kristin Qian","orcid":null,"position":6,"is_corresponding":false},{"id":23988,"name":"Brittany C. Michel","orcid":null,"position":7,"is_corresponding":false},{"id":3630,"name":"Jason D. Buenrostro","orcid":"0000-0001-9958-3987","position":8,"is_corresponding":false},{"id":3585,"name":"Bonnie Berger","orcid":"0000-0002-2724-7228","position":9,"is_corresponding":false},{"id":29633,"name":"Prisca Liberali","orcid":"0000-0003-0695-6081","position":10,"is_corresponding":false},{"id":23989,"name":"Cigall Kadoch","orcid":"0000-0002-4058-5985","position":11,"is_corresponding":false},{"id":23983,"name":"Jordan E. Otto","orcid":null,"position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","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":[]}