{"doi":"10.4049/jimmunol.2000015","title":"Cutting Edge: Hypoxia-Induced Ubc9 Promoter Hypermethylation Regulates IL-17 Expression in Ulcerative Colitis","abstract":"Abstract Dysregulated IL-17 expression is central to the pathogenesis of several inflammatory disorders, including ulcerative colitis. We have shown earlier that SUMOylation of ROR-γt, the transcription factor for IL-17, regulates colonic inflammation. In this study, we show that the expression of Ubc9, the E2 enzyme that targets ROR-γt for SUMOylation, is significantly reduced in the colonic mucosa of ulcerative colitis patients. Mechanistically, we demonstrate that hypoxia-inducible factor 1α (HIF-1α) binds to a CpG island within the Ubc9 gene promoter, resulting in its hypermethylation and reduced Ubc9 expression. CRISPR–Cas9-mediated inhibition of HIF-1α normalized Ubc9 and attenuated IL-17 expression in Th17 cells and reduced diseases severity in Rag1−/− mice upon adoptive transfer. Collectively, our study reveals a novel epigenetic mechanism of regulation of ROR-γt that could be exploited in inflammatory diseases.","journal":"The Journal of Immunology","year":2021,"id":199714,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":628813,"name":"Amir Kumar Singh","orcid":"0000-0003-2814-2759","position":1,"is_corresponding":false},{"id":414622,"name":"Petro Starokadomskyy","orcid":"0000-0002-9848-9187","position":2,"is_corresponding":false},{"id":266671,"name":"Weibo Luo","orcid":"0000-0002-1992-0320","position":3,"is_corresponding":false},{"id":266693,"name":"Arianne L. Theiss","orcid":"0000-0003-2862-0933","position":4,"is_corresponding":false},{"id":319713,"name":"Ezra Burstein","orcid":"0000-0003-4341-6367","position":5,"is_corresponding":false},{"id":269153,"name":"K. Venuprasad","orcid":null,"position":6,"is_corresponding":false},{"id":626345,"name":"Ritesh Kumar","orcid":"0000-0002-0150-8880","position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":null,"created_at":"2026-07-18T23:50:40.558460Z","pmid":"33504619","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":[]}