{"doi":"10.1038/s41467-021-26159-1","title":"Tcf1 and Lef1 provide constant supervision to mature CD8+ T cell identity and function by organizing genomic architecture","abstract":"Abstract T cell identity is established during thymic development, but how it is maintained in the periphery remains unknown. Here we show that ablating Tcf1 and Lef1 transcription factors in mature CD8 + T cells aberrantly induces genes from non-T cell lineages. Using high-throughput chromosome-conformation-capture sequencing, we demonstrate that Tcf1/Lef1 are important for maintaining three-dimensional genome organization at multiple scales in CD8 + T cells. Comprehensive network analyses coupled with genome-wide profiling of chromatin accessibility and Tcf1 occupancy show the direct impact of Tcf1/Lef1 on the T cell genome is to promote formation of extensively interconnected hubs through enforcing chromatin interaction and accessibility. The integrative mechanisms utilized by Tcf1/Lef1 underlie activation of T cell identity genes and repression of non-T lineage genes, conferring fine control of various T cell functionalities. These findings suggest that Tcf1/Lef1 control global genome organization and help form intricate chromatin-interacting hubs to facilitate promoter-enhancer/silencer contact, hence providing constant supervision of CD8 + T cell identity and function.","journal":"Nature Communications","year":2021,"id":150127,"datarank":0.6907755278982138,"base_score":4.605170185988092,"endowment":4.605170185988092,"self_citation_contribution":0.6907755278982138,"citation_network_contribution":0.0,"self_endowment_contribution":0.6907755278982138,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":99,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"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":373436,"name":"Xiang Li","orcid":"0000-0002-8931-3681","position":1,"is_corresponding":false},{"id":638370,"name":"Xia Chen","orcid":"0000-0003-2177-7591","position":2,"is_corresponding":false},{"id":375086,"name":"Zhouhao Zeng","orcid":null,"position":3,"is_corresponding":false},{"id":353156,"name":"Shaoqi Zhu","orcid":"0000-0001-9509-3526","position":4,"is_corresponding":false},{"id":477859,"name":"Kexin Gai","orcid":null,"position":5,"is_corresponding":false},{"id":317054,"name":"Weiqun Peng","orcid":"0000-0001-5521-9091","position":6,"is_corresponding":false},{"id":271042,"name":"Hai‐Hui Xue","orcid":"0000-0002-9163-7669","position":7,"is_corresponding":false},{"id":286407,"name":"Qiang Shan","orcid":"0000-0002-7089-0278","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:43:01.325389Z","pmid":"34615872","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":[]}