{"doi":"10.1084/jem.20202012","title":"The histone demethylase Lsd1 regulates multiple repressive gene programs during T cell development","abstract":"Analysis of the transcriptional profiles of developing thymocytes has shown that T lineage commitment is associated with loss of stem cell and early progenitor gene signatures and the acquisition of T cell gene signatures. Less well understood are the epigenetic alterations that accompany or enable these transcriptional changes. Here, we show that the histone demethylase Lsd1 (Kdm1a) performs a key role in extinguishing stem/progenitor transcriptional programs in addition to key repressive gene programs during thymocyte maturation. Deletion of Lsd1 caused a block in late T cell development and resulted in overexpression of interferon response genes as well as genes regulated by the Gfi1, Bcl6, and, most prominently, Bcl11b transcriptional repressors in CD4+CD8+ thymocytes. Transcriptional overexpression in Lsd1-deficient thymocytes was not always associated with increased H3K4 trimethylation at gene promoters, indicating that Lsd1 indirectly affects the expression of many genes. Together, these results identify a critical function for Lsd1 in the epigenetic regulation of multiple repressive gene signatures during T cell development.","journal":"The Journal of Experimental Medicine","year":2021,"id":183640,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9479,"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":737451,"name":"Lauren Clubb","orcid":"0000-0003-1480-7043","position":1,"is_corresponding":false},{"id":264037,"name":"Apratim Mitra","orcid":"0000-0003-3279-0054","position":2,"is_corresponding":false},{"id":299366,"name":"Laura B. Chopp","orcid":"0000-0001-6494-4439","position":3,"is_corresponding":false},{"id":712679,"name":"Jia Nie","orcid":"0000-0002-3865-0143","position":4,"is_corresponding":false},{"id":366403,"name":"Yi Ding","orcid":"0000-0002-1958-8524","position":5,"is_corresponding":false},{"id":737452,"name":"Arundhoti Das","orcid":"0000-0001-8574-9368","position":6,"is_corresponding":false},{"id":737453,"name":"Harini Venkataganesh","orcid":"0000-0001-6831-6368","position":7,"is_corresponding":false},{"id":737454,"name":"Jan Lee","orcid":"0000-0002-7393-2533","position":8,"is_corresponding":false},{"id":381654,"name":"Dalal El‐Khoury","orcid":"0000-0002-0239-6462","position":9,"is_corresponding":false},{"id":737455,"name":"LiQi Li","orcid":"0000-0002-3173-2330","position":10,"is_corresponding":false},{"id":471420,"name":"Avinash Bhandoola","orcid":"0000-0002-4657-8372","position":11,"is_corresponding":false},{"id":299371,"name":"Rémy Bosselut","orcid":"0000-0003-2033-1790","position":12,"is_corresponding":false},{"id":341213,"name":"Paul E. Love","orcid":"0000-0002-6682-7372","position":13,"is_corresponding":false},{"id":381653,"name":"Daniel B. Stamos","orcid":"0000-0002-9646-0831","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T23:48:22.008011Z","pmid":"34726730","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":[]}