{"doi":"10.1101/2022.11.18.516445","title":"Distinct super-enhancer elements differentially control <i>Il2ra</i> gene expression in a cell-type specific fashion","abstract":"Summary The IL-2 receptor α-chain (IL-2Rα/CD25) is constitutively expressed on DN2/DN3 thymocytes and Treg cells but induced by IL-2 on mature T and NK cells. Il2ra expression is regulated by a super-enhancer extensively bound by STAT5 in mature T cells. Here, we demonstrate that STAT5 cooperates with Notch to induce/maintain Il2ra/ CD25 expression in DN2/DN3 cells. Moreover, we systematically investigated CD25 regulation 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 Tregs, whereas deleting an intronic region primarily decreased IL-2-induced CD25 on peripheral T and NK cells. Thus, distinct elements preferentially control constitutive versus inducible expression in a cell-type-specific manner, with the MED1 coactivator co-localizing with specific STAT5 binding sites. Moreover, the intronic region was a dominant element whose deletion altered the structure throughout the super-enhancer in mature T cells. These results demonstrate differential functions for distinct super-enhancer elements, thereby indicating ways to manipulate CD25 expression in a cell-type specific fashion.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":304899,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","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":242699,"name":"Chengyu Liu","orcid":"0000-0002-5136-9225","position":4,"is_corresponding":false},{"id":626833,"name":"Jangsuk Oh","orcid":null,"position":5,"is_corresponding":false},{"id":998325,"name":"Min Ren","orcid":"0000-0002-8414-7661","position":6,"is_corresponding":false},{"id":998326,"name":"Yutaka Enomoto","orcid":"0000-0002-6346-9362","position":7,"is_corresponding":false},{"id":278215,"name":"Erin E. West","orcid":"0000-0002-7103-8394","position":8,"is_corresponding":false},{"id":439836,"name":"Stephen M. Christensen","orcid":"0000-0002-3618-6420","position":9,"is_corresponding":false},{"id":379415,"name":"Chi‐Keung Wan","orcid":"0000-0003-4783-3029","position":10,"is_corresponding":false},{"id":998327,"name":"Meili Ge","orcid":"0000-0002-8229-4203","position":11,"is_corresponding":false},{"id":650550,"name":"Jian‐Xin Lin","orcid":null,"position":12,"is_corresponding":false},{"id":110385,"name":"Pandurangan Vijayanand","orcid":"0000-0001-7067-9723","position":13,"is_corresponding":false},{"id":699594,"name":"Ellen V. Rothenberg","orcid":"0000-0002-3901-347X","position":14,"is_corresponding":false},{"id":625483,"name":"Warren J. Leonard","orcid":"0000-0002-5740-7448","position":15,"is_corresponding":false},{"id":625474,"name":"Rosanne Spolski","orcid":"0009-0002-1511-9349","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T00:32:37.185846Z","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":[]}