{"doi":"10.1016/j.ccell.2020.03.001","title":"Loss of CHD1 Promotes Heterogeneous Mechanisms of Resistance to AR-Targeted Therapy via Chromatin Dysregulation","abstract":"Metastatic prostate cancer is characterized by recurrent genomic copy number alterations that are presumed to contribute to resistance to hormone therapy. We identified CHD1 loss as a cause of antiandrogen resistance in an in vivo small hairpin RNA (shRNA) screen of 730 genes deleted in prostate cancer. ATAC-seq and RNA-seq analyses showed that CHD1 loss resulted in global changes in open and closed chromatin with associated transcriptomic changes. Integrative analysis of this data, together with CRISPR-based functional screening, identified four transcription factors (NR3C1, POU3F2, NR2F1, and TBX2) that contribute to antiandrogen resistance, with associated activation of non-luminal lineage programs. Thus, CHD1 loss results in chromatin dysregulation, thereby establishing a state of transcriptional plasticity that enables the emergence of antiandrogen resistance through heterogeneous mechanisms.","journal":"Cancer Cell","year":2020,"id":51140,"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":166,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"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":254505,"name":"Chuanli Zhou","orcid":"0000-0003-1848-2055","position":1,"is_corresponding":false},{"id":254506,"name":"Xiaoling Li","orcid":"0000-0002-1554-1569","position":2,"is_corresponding":false},{"id":238286,"name":"Spencer Barnes","orcid":"0000-0003-1103-0953","position":3,"is_corresponding":false},{"id":254507,"name":"Su Deng","orcid":"0000-0002-0835-2452","position":4,"is_corresponding":false},{"id":254508,"name":"Elizabeth Hoover","orcid":"0000-0002-6215-2830","position":5,"is_corresponding":false},{"id":256920,"name":"Chi-Chao Chen","orcid":null,"position":6,"is_corresponding":false},{"id":238280,"name":"Young Sun Lee","orcid":"0000-0002-6612-7341","position":7,"is_corresponding":false},{"id":21276,"name":"Yanxiao Zhang","orcid":"0000-0001-9618-637X","position":8,"is_corresponding":false},{"id":254509,"name":"Choushi Wang","orcid":"0000-0002-6667-1689","position":9,"is_corresponding":false},{"id":254510,"name":"Lauren A. 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