{"doi":"10.1101/2024.02.08.579505","title":"NF-κB Signaling is Required for X-Chromosome Inactivation Maintenance Following T cell Activation","abstract":"RNA and heterochromatic modifications on the inactive X chromosome (Xi), and these modifications become enriched at the Xi after cell stimulation. Here, we examined allele-specific gene expression and the epigenomic profiles of the Xi following T cell stimulation. We found that the Xi in unstimulated T cells is largely dosage compensated and is enriched with the repressive H3K27me3 modification, but not the H2AK119-ubiquitin (Ub) mark, even at promoters of XCI escape genes. Upon CD3/CD28-mediated T cell stimulation, the Xi accumulates H2AK119-Ub and H3K27me3 across the Xi. Next, we examined the T cell signaling pathways responsible for Xist RNA localization to the Xi and found that T cell receptor (TCR) engagement, specifically NF-κB signaling downstream of TCR, is required. Disruption of NF-κB signaling, using inhibitors or genetic deletions, in mice and patients with immunodeficiencies prevents Xist/XIST RNA accumulation at the Xi and alters expression of some X-linked genes. Our findings reveal a novel connection between NF-κB signaling pathways which impact XCI maintenance in female T cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":489988,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1045648,"name":"Natalie E. Toothacre","orcid":"0000-0002-4500-7965","position":1,"is_corresponding":false},{"id":857895,"name":"Nikhil Jiwrajka","orcid":"0000-0003-1630-1767","position":2,"is_corresponding":false},{"id":1241119,"name":"Amanda M. Driscoll","orcid":null,"position":3,"is_corresponding":false},{"id":563022,"name":"Lindsey A. Shallberg","orcid":"0000-0001-6573-7327","position":4,"is_corresponding":false},{"id":104929,"name":"Charlotte Cunningham‐Rundles","orcid":"0000-0003-0725-0320","position":5,"is_corresponding":false},{"id":454864,"name":"Sara Barmettler","orcid":"0000-0001-8188-9187","position":6,"is_corresponding":false},{"id":108358,"name":"Jocelyn R. Farmer","orcid":"0000-0003-4901-9848","position":7,"is_corresponding":false},{"id":325555,"name":"James Verbsky","orcid":"0000-0001-6682-1002","position":8,"is_corresponding":false},{"id":325556,"name":"John M. Routes","orcid":"0000-0001-8378-3773","position":9,"is_corresponding":false},{"id":276893,"name":"Daniel P. Beiting","orcid":"0000-0002-2865-4589","position":10,"is_corresponding":false},{"id":285501,"name":"Neil Romberg","orcid":"0000-0002-1881-5318","position":11,"is_corresponding":false},{"id":242811,"name":"Michael J. May","orcid":"0000-0002-2485-3716","position":12,"is_corresponding":false},{"id":376544,"name":"Montserrat C. Anguera","orcid":"0000-0003-4992-3079","position":13,"is_corresponding":false},{"id":341286,"name":"Katherine S. Forsyth","orcid":"0000-0002-4991-1601","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T02:08:32.775003Z","pmid":"38405871","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":[]}