{"doi":"10.1093/nar/gkaa098","title":"Alteration of CTCF-associated chromatin neighborhood inhibits TAL1-driven oncogenic transcription program and leukemogenesis","abstract":"Aberrant activation of the TAL1 is associated with up to 60% of T-ALL cases and is involved in CTCF-mediated genome organization within the TAL1 locus, suggesting that CTCF boundary plays a pathogenic role in T-ALL. Here, we show that -31-Kb CTCF binding site (-31CBS) serves as chromatin boundary that defines topologically associating domain (TAD) and enhancer/promoter interaction required for TAL1 activation. Deleted or inverted -31CBS impairs TAL1 expression in a context-dependent manner. Deletion of -31CBS reduces chromatin accessibility and blocks long-range interaction between the +51 erythroid enhancer and TAL1 promoter-1 leading to inhibition of TAL1 expression in erythroid cells, but not T-ALL cells. However, in TAL1-expressing T-ALL cells, the leukemia-prone TAL1 promoter-IV specifically interacts with the +19 stem cell enhancer located 19 Kb downstream of TAL1 and this interaction is disrupted by the -31CBS inversion in T-ALL cells. Inversion of -31CBS in Jurkat cells alters chromatin accessibility, histone modifications and CTCF-mediated TAD leading to inhibition of TAL1 expression and TAL1-driven leukemogenesis. Thus, our data reveal that -31CBS acts as critical regulator to define +19-enhancer and the leukemic prone promoter IV interaction for TAL1 activation in T-ALL. Manipulation of CTCF boundary can alter TAL1 TAD and oncogenic transcription networks in leukemogenesis.","journal":"Nucleic Acids Research","year":2020,"id":63423,"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":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"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":335204,"name":"Ziwei Liao","orcid":"0000-0001-8405-9293","position":1,"is_corresponding":false},{"id":335205,"name":"Huacheng Luo","orcid":"0000-0002-5844-8890","position":2,"is_corresponding":false},{"id":335206,"name":"Aissa Benyoucef","orcid":"0000-0003-1369-6820","position":3,"is_corresponding":false},{"id":335207,"name":"Yuanyuan Kang","orcid":"0000-0001-8279-9490","position":4,"is_corresponding":false},{"id":335208,"name":"Qian Lai","orcid":"0000-0002-4282-7757","position":5,"is_corresponding":false},{"id":307567,"name":"Sinisa Dovat","orcid":"0000-0003-3906-6165","position":6,"is_corresponding":false},{"id":307569,"name":"Barbara A. Miller","orcid":"0000-0002-9313-4686","position":7,"is_corresponding":false},{"id":335209,"name":"Iouri Chepelev","orcid":"0000-0002-2121-8805","position":8,"is_corresponding":false},{"id":335210,"name":"Yangqiu Li","orcid":"0000-0002-0974-4036","position":9,"is_corresponding":false},{"id":233091,"name":"Keji Zhao","orcid":"0000-0001-5559-6233","position":10,"is_corresponding":false},{"id":335211,"name":"Marjorie Brand","orcid":"0000-0001-8915-8012","position":11,"is_corresponding":false},{"id":335212,"name":"Suming Huang","orcid":"0000-0002-4788-2085","position":12,"is_corresponding":false},{"id":230195,"name":"Ying Li","orcid":"0000-0002-9316-2521","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T21:11:00.632961Z","pmid":"32086528","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":[]}