{"doi":"10.1093/nar/gkaf629","title":"EBNA leader protein orchestrates chromatin architecture remodeling during Epstein-Barr virus-induced B cell transformation","abstract":"Epstein-Barr virus Nuclear Antigen Leader Protein (EBNA-LP) plays a pivotal role in the transformation of B cells by Epstein-Barr virus (EBV), functioning independently of EBNA2 to regulate chromatin architecture and gene expression. Our study reveals that EBNA-LP binds to chromatin regions distinct from EBNA2 and facilitates the formation of long-distance chromatin loops by interacting with the cellular factor YY1. This interaction reconfigures the three-dimensional structure of the host genome, enhancing the integrity of topologically associating domains (TADs) and promoting the interaction between enhancers and promoters within these domains. In EBV-infected B cells, EBNA-LP strengthens YY1-mediated chromatin loops within TADs, which helps maintain stable regulatory programs essential for B cell transformation. Notably, EBNA-LP is crucial for establishing EBV-induced enhancers, yet it is not required for their maintenance once formed. Additionally, our data suggest a compensatory increase in CTCF binding in the absence of EBNA-LP, leading to more promiscuous chromatin interactions between TADs and a reduced TAD insulation at their boundaries. These findings provide new insights into the molecular mechanisms by which EBV reshapes the host genome chromatin architecture to support B cell transformation and highlight potential therapeutic targets for disrupting EBV-driven oncogenesis.","journal":"Nucleic Acids Research","year":2025,"id":521544,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":325823,"name":"Lisa Beatrice Caruso","orcid":"0000-0003-4248-0551","position":1,"is_corresponding":false},{"id":572395,"name":"Jana M. Cable","orcid":"0000-0001-9267-611X","position":2,"is_corresponding":false},{"id":1392387,"name":"Rachel Sklutuis","orcid":null,"position":3,"is_corresponding":false},{"id":815253,"name":"Sarah Preston‐Alp","orcid":"0000-0001-6807-2244","position":4,"is_corresponding":false},{"id":1248927,"name":"Robert E. White","orcid":"0000-0002-5115-2173","position":5,"is_corresponding":false},{"id":395715,"name":"Micah A. Luftig","orcid":"0000-0002-2964-1907","position":6,"is_corresponding":false},{"id":325824,"name":"Italo Tempera","orcid":"0000-0001-7893-2914","position":7,"is_corresponding":false},{"id":910711,"name":"Davide Maestri","orcid":null,"position":0,"is_corresponding":true}],"reference_count":98,"raw_metadata":null,"created_at":"2026-07-19T02:49:44.558743Z","pmid":"40598900","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":[]}