{"doi":"10.1101/2020.09.17.302596","title":"YY1 cistrome analysis uncovers an essential requirement of the YY1:BRD4-PFKP regulatory axis for promoting tumorigenesis of castration-resistant prostate cancer","abstract":"Abstract Castration-resistant prostate cancer (CRPC) is a terminal disease, demanding a better understanding of its pathogenesis. Targeted therapy needs to be developed for CRPC due to its heterogeneity and resistance to current treatments. Here, through cistrome study of YY1, a transcription factor significantly overexpressed during prostate cancer progression, we identify a YY1-PFKP axis to be essential for CRPC tumorigenesis. Depletion of YY1 in independent CRPC models dramatically reduced tumor cell growth in vitro and delayed oncogenic progression in vivo . Importantly, YY1 functions as a master regulator of prostate tumor metabolism including the Warburg effect and mitochondria respiration. Loss-of-function and rescue studies further reveals a mechanistic underpinning in which YY1 directly binds and trans-activates PFKP , a gene encoding the rate-limiting enzyme for glycolysis, significantly contributing to the YY1-enforced oncogenic phenotypes such as enhanced tumor cell glycolysis and malignant growth. Additionally, a vast majority of gene-regulatory element in advanced prostate cancer cells are bound by YY1, lending a support for its role as a master regulator of prostate cancer progression. YY1 interactome studies point to bromodomain-containing coactivators in prostate cancer, which act as functional partners of YY1 to potentiate YY1-related target gene activation. Altogether, this study unveils an unexplored YY1:BRD4-PFKP oncogenic axis operating in advanced prostate cancer with implications for therapy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":131041,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.953,"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":584347,"name":"Yi‐Hsuan Tsai","orcid":"0000-0002-8891-3124","position":1,"is_corresponding":false},{"id":584348,"name":"Phillip M. Galbo","orcid":"0000-0002-5391-598X","position":2,"is_corresponding":false},{"id":574884,"name":"Weida Gong","orcid":"0000-0002-0046-9277","position":3,"is_corresponding":false},{"id":245937,"name":"Aaron J. Storey","orcid":"0000-0003-4089-5008","position":4,"is_corresponding":false},{"id":584349,"name":"Yuemei Xu","orcid":"0000-0002-0223-7146","position":5,"is_corresponding":false},{"id":244704,"name":"Stephanie D. Byrum","orcid":"0000-0002-1783-3610","position":6,"is_corresponding":false},{"id":354013,"name":"Young E. Whang","orcid":"0000-0002-1621-6661","position":7,"is_corresponding":false},{"id":13902,"name":"Joel S. Parker","orcid":"0000-0003-2080-6901","position":8,"is_corresponding":false},{"id":342237,"name":"Samuel G. Mackintosh","orcid":"0000-0002-5530-8403","position":9,"is_corresponding":false},{"id":349306,"name":"Ricky D. Edmondson","orcid":null,"position":10,"is_corresponding":false},{"id":379499,"name":"Alan J. Tackett","orcid":"0000-0002-3672-4460","position":11,"is_corresponding":false},{"id":290797,"name":"Jiaoti Huang","orcid":"0000-0003-1195-1998","position":12,"is_corresponding":false},{"id":284103,"name":"Deyou Zheng","orcid":"0000-0003-4354-5337","position":13,"is_corresponding":false},{"id":304429,"name":"H. Shelton Earp","orcid":"0000-0003-1229-4619","position":14,"is_corresponding":false},{"id":247178,"name":"Gang Greg Wang","orcid":"0000-0002-7210-9940","position":15,"is_corresponding":false},{"id":273494,"name":"Ling Cai","orcid":"0000-0002-8592-5269","position":16,"is_corresponding":false},{"id":584346,"name":"Chenxi Xu","orcid":"0000-0001-7747-0033","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:16:00.235845Z","pmid":null,"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":[]}