{"doi":"10.1101/2020.06.13.150177","title":"The transcription factor STAT5 binds to distinct super-enhancer sites and controls <i>Lrrc32</i> expression in a prominent autoimmune and allergic disease risk locus","abstract":"Summary Genetic variants associated with diseases are enriched in genomic sequences linked to regulatory regions, such as enhancers, super-enhancers and possibly repressors, that control nearby and distant genes. A known allergic and autoimmune risk locus at chromosome 11q13.5 1,2 is associated with the LRRC32 gene, which encodes GARP, a protein critical for TGF-β delivery 3 . This region coincides with a candidate enhancer that was predicted by the presence of activating chromatin marks and contains a polymorphism significantly associated with GARP expression on CD4 + CD127 - CD25 + T reg cells 4 . In the mouse, binding of the cytokine-induced transcription factor STAT5 was detected at two sites within the expansive candidate enhancer region and a 2.3 kb deletion resulted in reduced Lrrc32 expression 4 . However, a clear definition of the enhancer units controlled by STAT5 and a functional understanding of STAT5 in the regulation of Lrrc32 are needed. Here we use high-resolution ChIP-seq and identify three STAT5 binding sites within the Lrrc32 super-enhancer, one shared between T reg cells and mammary epithelium and one specific to each respective cell type. Using mice that express only 10% of normal STAT5 levels we demonstrate the defining contribution of STAT5 in the activation of the Lrrc32 super-enhancer.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126924,"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":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":279569,"name":"Hye‐Kyung Lee","orcid":"0000-0002-7785-5942","position":1,"is_corresponding":false},{"id":14888,"name":"Lothar Hennighausen","orcid":"0000-0001-8319-9841","position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":null,"created_at":"2026-07-18T23:15:27.226519Z","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":[]}