{"doi":"10.1126/sciimmunol.adi8217","title":"Distinct use of super-enhancer elements controls cell type–specific CD25 transcription and function","abstract":"The IL-2 receptor α chain (IL-2Rα/CD25) is constitutively expressed on double-negative (DN2/DN3 thymocytes and regulatory T cells (T regs ) but induced by IL-2 on T and natural killer (NK) cells, with Il2ra expression regulated by a STAT5-dependent super-enhancer. We investigated CD25 regulation and function using a series of mice with deletions spanning STAT5-binding elements. Deleting the upstream super-enhancer region mainly affected constitutive CD25 expression on DN2/DN3 thymocytes and T regs , with these mice developing autoimmune alopecia, whereas deleting an intronic region decreased IL-2–induced CD25 on peripheral T and NK cells. Thus, distinct super-enhancer elements preferentially control constitutive versus inducible expression in a cell type–specific manner. The mediator-1 coactivator colocalized with specific STAT5-binding sites. Moreover, both upstream and intronic regions had extensive chromatin interactions, and deletion of either region altered the super-enhancer structure in mature T cells. These results demonstrate differential functions for distinct super-enhancer elements, thereby indicating previously unknown ways to manipulate CD25 expression in a cell type–specific fashion.","journal":"Science Immunology","year":2023,"id":346986,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9593,"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":699138,"name":"Peng Li","orcid":"0000-0002-4721-5936","position":1,"is_corresponding":false},{"id":266581,"name":"Vivek Chandra","orcid":"0000-0002-4047-015X","position":2,"is_corresponding":false},{"id":253536,"name":"Boyoung Shin","orcid":"0000-0001-7926-5527","position":3,"is_corresponding":false},{"id":327423,"name":"Shubham Goel","orcid":null,"position":4,"is_corresponding":false},{"id":246523,"name":"Keiko Sakamoto","orcid":"0000-0001-8957-3232","position":5,"is_corresponding":false},{"id":242699,"name":"Chengyu Liu","orcid":"0000-0002-5136-9225","position":6,"is_corresponding":false},{"id":626833,"name":"Jangsuk Oh","orcid":null,"position":7,"is_corresponding":false},{"id":998325,"name":"Min Ren","orcid":"0000-0002-8414-7661","position":8,"is_corresponding":false},{"id":998326,"name":"Yutaka Enomoto","orcid":"0000-0002-6346-9362","position":9,"is_corresponding":false},{"id":278215,"name":"Erin E. West","orcid":"0000-0002-7103-8394","position":10,"is_corresponding":false},{"id":439836,"name":"Stephen M. Christensen","orcid":"0000-0002-3618-6420","position":11,"is_corresponding":false},{"id":379415,"name":"Chi‐Keung Wan","orcid":"0000-0003-4783-3029","position":12,"is_corresponding":false},{"id":998327,"name":"Meili Ge","orcid":"0000-0002-8229-4203","position":13,"is_corresponding":false},{"id":1087897,"name":"Jian-Xin Lin","orcid":"0000-0001-5849-9412","position":14,"is_corresponding":false},{"id":353367,"name":"Bingyu Yan","orcid":"0000-0003-4429-8200","position":15,"is_corresponding":false},{"id":278230,"name":"Majid Kazemian","orcid":"0000-0001-7080-8820","position":16,"is_corresponding":false},{"id":265814,"name":"Zu‐Xi Yu","orcid":"0000-0003-1141-4551","position":17,"is_corresponding":false},{"id":246528,"name":"Keisuke Nagao","orcid":"0000-0002-7005-3138","position":18,"is_corresponding":false},{"id":110385,"name":"Pandurangan Vijayanand","orcid":"0000-0001-7067-9723","position":19,"is_corresponding":false},{"id":699594,"name":"Ellen V. Rothenberg","orcid":"0000-0002-3901-347X","position":20,"is_corresponding":false},{"id":625483,"name":"Warren J. Leonard","orcid":"0000-0002-5740-7448","position":21,"is_corresponding":false},{"id":625474,"name":"Rosanne Spolski","orcid":"0009-0002-1511-9349","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T01:11:53.085356Z","pmid":"37922339","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":[]}