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However, BRD4 depletion/BRDT complementation revealed that BRDT can also release paused RNA polymerase II independently of its bromodomains as we previously demonstrated not to be required for Pol II pause/release function of BRD4, underscoring the functional importance of the C-terminal domains in both BRD4 and BRDT and their potential as therapeutic targets in solid tumors. Based on this study, future investigations should explore BRD4-distinct BRDT functions and BRDT misexpression driving cancer pathogenesis.</jats:p>","journal":"Science Advances","year":2025,"id":605067,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":552623,"name":"Marta Iwanaszko","orcid":"0000-0001-6909-5931","position":1,"is_corresponding":false},{"id":1552645,"name":"Shimaa Hassan AbdelAziz Soliman","orcid":null,"position":2,"is_corresponding":false},{"id":863188,"name":"Yukitomo Ishi","orcid":"0000-0003-4834-2619","position":3,"is_corresponding":false},{"id":1025162,"name":"Sarah Gold","orcid":"0000-0001-7390-4121","position":4,"is_corresponding":false},{"id":1552646,"name":"Ruxuan Qiu","orcid":"0009-0001-1140-4655","position":5,"is_corresponding":false},{"id":1103309,"name":"Benjamin C. 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BRDT knockdown in lung cancer cells slowed tumor growth and prolonged survival in a xenograft model. Comparative characterization of PTEFb complex participation and chromatin binding indicates BRD4-redundant and BRD4-distinct BRDT functions. Unlike dual depletion, individual BRD4 or BRDT knockdown did not impair transcriptional responses to hypoxia in BRDT-expressing cells, consistent with redundant function. However, BRD4 depletion/BRDT complementation revealed that BRDT can also release paused RNA polymerase II independently of its bromodomains as we previously demonstrated not to be required for Pol II pause/release function of BRD4, underscoring the functional importance of the C-terminal domains in both BRD4 and BRDT and their potential as therapeutic targets in solid tumors. 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