Dergi makalesi Açık Erişim
Huang, Chia-Chi Flora; Lingadahalli, Shreyas; Morova, Tunc; Ozturan, Dogancan; Hu, Eugene; Yu, Ivan Pak Lok; Linder, Simon; Hoogstraat, Marlous; Stelloo, Suzan; Sar, Funda; van der Poel, Henk; Altintas, Umut Berkay; Saffarzadeh, Mohammadali; Le Bihan, Stephane; McConeghy, Brian; Gokbayrak, Bengul; Feng, Felix Y.; Gleave, Martin E.; Bergman, Andries M.; Collins, Colin; Collins, Colin
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Once activated, the AR binds to cis-regulatory enhancer elements on DNA that drive gene expression. Yet, there are 10-100x more binding sites than differentially expressed genes. It is unclear how or if these excess binding sites impact gene transcription. Results To characterize the regulatory logic of AR-mediated transcription, we generated a locus-specific map of enhancer activity by functionally testing all common clinical AR binding sites with Self-Transcribing Active Regulatory Regions sequencing (STARRseq). Only 7% of AR binding sites displayed androgen-dependent enhancer activity. Instead, the vast majority of AR binding sites were either inactive or constitutively active enhancers. These annotations strongly correlated with enhancer-associated features of both in vitro cell lines and clinical prostate cancer samples. Evaluating the effect of each enhancer class on transcription, we found that AR-regulated enhancers frequently interact with promoters and form central chromosomal loops that are required for transcription. Somatic mutations of these critical AR-regulated enhancers often impact enhancer activity. Conclusions Using a functional map of AR enhancer activity, we demonstrated that AR-regulated enhancers act as a regulatory hub that increases interactions with other AR binding sites and gene promoters.", "doi": "10.1186/s13059-021-02339-6", "has_grant": false, "journal": { "issue": "1", "title": "GENOME BIOLOGY", "volume": "22" }, "license": { "id": "cc-by" }, "publication_date": "2021-01-01", "relations": { "version": [ { "count": 1, "index": 0, "is_last": true, "last_child": { "pid_type": "recid", "pid_value": "234974" }, "parent": { "pid_type": "recid", "pid_value": "234973" } } ] }, "resource_type": { "subtype": "article", "title": "Dergi makalesi", "type": "publication" }, "science_branches": [ "Di\u011fer" ], "title": "Functional mapping of androgen receptor enhancer activity" }, "owners": [ 1 ], "revision": 1, "stats": { "downloads": 4.0, "unique_downloads": 4.0, "unique_views": 84.0, "version_downloads": 4.0, "version_unique_downloads": 4.0, "version_unique_views": 84.0, "version_views": 86.0, "version_volume": 1404.0, "views": 86.0, "volume": 1404.0 }, "updated": "2022-10-07T09:11:57.974809+00:00" }
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