{"doi":"10.1172/jci158419","title":"The SWI/SNF chromatin-remodeling subunit DPF2 facilitates NRF2-dependent antiinflammatory and antioxidant gene expression","abstract":"During emergency hematopoiesis, hematopoietic stem cells (HSCs) rapidly proliferate to produce myeloid and lymphoid effector cells, a response that is critical against infection or tissue injury. If unresolved, this process leads to sustained inflammation, which can cause life-threatening diseases and cancer. Here, we identify a role of double PHD fingers 2 (DPF2) in modulating inflammation. DPF2 is a defining subunit of the hematopoiesis-specific BAF (SWI/SNF) chromatin-remodeling complex, and it is mutated in multiple cancers and neurological disorders. We uncovered that hematopoiesis-specific Dpf2-KO mice developed leukopenia, severe anemia, and lethal systemic inflammation characterized by histiocytic and fibrotic tissue infiltration resembling a clinical hyperinflammatory state. Dpf2 loss impaired the polarization of macrophages responsible for tissue repair, induced the unrestrained activation of Th cells, and generated an emergency-like state of HSC hyperproliferation and myeloid cell-biased differentiation. Mechanistically, Dpf2 deficiency resulted in the loss of the BAF catalytic subunit BRG1 from nuclear factor erythroid 2-like 2-controlled (NRF2-controlled) enhancers, impairing the antioxidant and antiinflammatory transcriptional response needed to modulate inflammation. Finally, pharmacological reactivation of NRF2 suppressed the inflammation-mediated phenotypes and lethality of Dpf2Δ/Δ mice. Our work establishes an essential role of the DPF2-BAF complex in licensing NRF2-dependent gene expression in HSCs and immune effector cells to prevent chronic inflammation.","journal":"Journal of Clinical Investigation","year":2023,"id":336259,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":307349,"name":"Na Man","orcid":"0000-0002-1566-2192","position":1,"is_corresponding":false},{"id":616116,"name":"Yuichiro Nakata","orcid":"0000-0002-6852-4201","position":2,"is_corresponding":false},{"id":1067149,"name":"Concepcion Martinez-Caja","orcid":null,"position":3,"is_corresponding":false},{"id":309653,"name":"Daniel Karl","orcid":null,"position":4,"is_corresponding":false},{"id":265865,"name":"Felipe Beckedorff","orcid":"0000-0001-6735-6851","position":5,"is_corresponding":false},{"id":1066687,"name":"Francesco Tamiro","orcid":"0000-0002-5719-7276","position":6,"is_corresponding":false},{"id":267223,"name":"Chuan Chen","orcid":"0000-0001-5701-0857","position":7,"is_corresponding":false},{"id":746593,"name":"Stéphanie Duffort","orcid":null,"position":8,"is_corresponding":false},{"id":746008,"name":"Hidehiro Itonaga","orcid":"0000-0003-1438-3623","position":9,"is_corresponding":false},{"id":307350,"name":"Adnan K. Mookhtiar","orcid":"0000-0002-5110-4518","position":10,"is_corresponding":false},{"id":730787,"name":"Kranthi Kunkalla","orcid":null,"position":11,"is_corresponding":false},{"id":246356,"name":"Alfredo M. Valencia","orcid":"0000-0003-2432-9890","position":12,"is_corresponding":false},{"id":573661,"name":"Clayton K. Collings","orcid":"0000-0002-3471-2132","position":13,"is_corresponding":false},{"id":23989,"name":"Cigall Kadoch","orcid":"0000-0002-4058-5985","position":14,"is_corresponding":false},{"id":355510,"name":"Francisco Vega","orcid":"0000-0001-5956-452X","position":15,"is_corresponding":false},{"id":29973,"name":"Scott C. Kogan","orcid":"0000-0002-2395-8479","position":16,"is_corresponding":false},{"id":44604,"name":"Ramin Shiekhattar","orcid":"0000-0002-7943-7277","position":17,"is_corresponding":false},{"id":616118,"name":"Lluís Morey","orcid":"0000-0001-9851-4066","position":18,"is_corresponding":false},{"id":675334,"name":"Daniel Bilbao","orcid":"0000-0003-1630-8811","position":19,"is_corresponding":false},{"id":353125,"name":"Stephen D. 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