{"doi":"10.1016/j.celrep.2025.116344","title":"GATA2 decommissioning of enhancers: A mechanism to constrain inflammatory signaling","abstract":"GATA2 establishes transcriptomes governing hematopoietic stem/progenitor cell development. In progenitors, GATA2 represses inflammatory genes ( Il6st and Il6ra ) encoding IL6ST/GP130 and IL6RA receptor subunits mediating IL-6 signaling. While IL6ST heterodimerizes with IL6RA, IL-11, IL-27, oncostatin M, and leukemia inhibitory factor receptors, IL6RA heterodimerizes exclusively with IL6ST to confer IL-6 signaling. As GATA2-dependent repression is not well understood, we devised a multi-omics strategy to elucidate mechanisms underlying repression and applied the approach to the cytokine/chemokine receptor gene family. Identifying accessible distal and intronic chromatin sites in GATA2-deficient (GATA2 low ), but not wild-type, progenitors unveiled that GATA2 represses Il6st and Il6ra enhancers. GATA2 loss instigates a chromatin transition to increase accessibility, occupancy by the hematopoietic activator PU.1, transcription, and cell signaling capacity. Ablating Il6st enhancers in GATA2 low cells abrogates Il6st expression and IL-6 and IL-27 signaling. Il6ra enhancer loss selectively abrogates Il6ra expression and IL-6 signaling. Thus, GATA2 decommissions enhancers to constrain inflammatory signaling.","journal":"Cell Reports","year":2025,"id":534844,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1106793,"name":"Vu L. Tran","orcid":"0000-0001-5320-3280","position":1,"is_corresponding":false},{"id":63630,"name":"Yue Xiong","orcid":"0000-0003-2744-6566","position":2,"is_corresponding":false},{"id":459567,"name":"Kirby D. Johnson","orcid":"0000-0003-0236-7482","position":3,"is_corresponding":false},{"id":438088,"name":"Koichi R. Katsumura","orcid":"0000-0002-1523-0533","position":4,"is_corresponding":false},{"id":459568,"name":"Peng Liu","orcid":"0000-0001-5655-2259","position":5,"is_corresponding":false},{"id":42934,"name":"Emery H. Bresnick","orcid":null,"position":6,"is_corresponding":false},{"id":1070442,"name":"Mabel M. Jung","orcid":"0000-0001-7258-2888","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T02:51:52.019261Z","pmid":"41004342","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":[]}