{"doi":"10.4049/jimmunol.1901311","title":"Identification of a Distal Locus Enhancer Element That Controls Cell Type–Specific <i>TNF</i> and <i>LTA</i> Gene Expression in Human T Cells","abstract":"Abstract The human TNF/LT locus genes TNF, LTA, and LTB are expressed in a cell type–specific manner. In this study, we show that a highly conserved NFAT binding site within the distal noncoding element hHS-8 coordinately controls TNF and LTA gene expression in human T cells. Upon activation of primary human CD4+ T cells, hHS-8 and the TNF and LTA promoters display increased H3K27 acetylation and nuclease sensitivity and coordinate induction of TNF, LTA, and hHS-8 enhancer RNA transcription occurs. Functional analyses using CRISPR/dead(d)Cas9 targeting of the hHS-8-NFAT site in the human T cell line CEM demonstrate significant reduction of TNF and LTA mRNA synthesis and of RNA polymerase II recruitment to their promoters. These studies elucidate how a distal element regulates the inducible cell type–specific gene expression program of the human TNF/LT locus and provide an approach for modulation of TNF and LTA transcription in human disease using CRISPR/dCas9.","journal":"The Journal of Immunology","year":2020,"id":88482,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"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":448799,"name":"Aya Nambu","orcid":"0000-0002-2797-6420","position":1,"is_corresponding":false},{"id":448800,"name":"Alla V. Tsytsykova","orcid":"0000-0003-4242-9828","position":2,"is_corresponding":false},{"id":450032,"name":"Shahin Ranjbar","orcid":null,"position":3,"is_corresponding":false},{"id":448801,"name":"Viraga Haridas","orcid":"0000-0001-9174-028X","position":4,"is_corresponding":false},{"id":51046,"name":"Laurens Kruidenier","orcid":null,"position":5,"is_corresponding":false},{"id":448802,"name":"David F. Tough","orcid":"0000-0003-3585-0649","position":6,"is_corresponding":false},{"id":450033,"name":"Anne E. Goldfeld","orcid":null,"position":7,"is_corresponding":false},{"id":450031,"name":"Luke D. Jasenosky","orcid":null,"position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-18T22:01:22.387926Z","pmid":"32978279","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":[]}