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dc.contributor.authorHsieh, Chen-Lin
dc.contributor.authorFei, Teng
dc.contributor.authorChen, Yiwen
dc.contributor.authorLi, Tiantian
dc.contributor.authorGao, Yanfei
dc.contributor.authorWang, Xiaodong
dc.contributor.authorSun, Tong
dc.contributor.authorSweeney, Christopher J
dc.contributor.authorLee, Gwo-Shu Mary
dc.contributor.authorChen, Shaoyong
dc.contributor.authorBalk, Steven Paul
dc.contributor.authorLiu, Xiaole (Shirley) Shirley
dc.contributor.authorBrown, Myles Avery
dc.contributor.authorKantoff, Philip Wayne
dc.date.accessioned2018-01-08T16:54:03Z
dc.date.issued2014
dc.identifier.citationHsieh, C.-L., T. Fei, Y. Chen, T. Li, Y. Gao, X. Wang, T. Sun, et al. 2014. “Enhancer RNAs Participate in Androgen Receptor-Driven Looping That Selectively Enhances Gene Activation.” Proceedings of the National Academy of Sciences 111 (20) (April 28): 7319–7324. doi:10.1073/pnas.1324151111.en_US
dc.identifier.issn0027-8424en_US
dc.identifier.issn1091-6490en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:34605060
dc.description.abstractThe androgen receptor (AR) is a key factor that regulates the behavior and fate of prostate cancer cells. The AR-regulated network is activated when AR binds enhancer elements and modulates specific enhancer–promoter looping. Kallikrein-related peptidase 3 (KLK3), which codes for prostate-specific antigen (PSA), is a well-known AR-regulated gene and its upstream enhancers produce bidirectional enhancer RNAs (eRNAs), termed KLK3e. Here, we demonstrate that KLK3e facilitates the spatial interaction of the KLK3 enhancer and the KLK2 promoter and enhances long-distance KLK2 transcriptional activation. KLK3e carries the core enhancer element derived from the androgen response element III (ARE III), which is required for the interaction of AR and Mediator 1 (Med1). Furthermore, we show that KLK3e processes RNA-dependent enhancer activity depending on the integrity of core enhancer elements. The transcription of KLK3e was detectable and its expression is significantly correlated with KLK3 \((R^2 = 0.6213, P < 5 × 10^{−11})\) and KLK2 \((R^2 = 0.5893, P < 5 × 10^{−10})\) in human prostate tissues. Interestingly, RNAi silencing of KLK3e resulted in a modest negative effect on prostate cancer cell proliferation. Accordingly, we report that an androgen-induced eRNA scaffolds the AR-associated protein complex that modulates chromosomal architecture and selectively enhances AR-dependent gene expression.en_US
dc.language.isoen_USen_US
dc.publisherProceedings of the National Academy of Sciencesen_US
dc.relation.isversionofdoi:10.1073/pnas.1324151111en_US
dash.licenseOAP
dc.subjectKLK3e/AR/Med1 complexen_US
dc.subjectchromosomal loopingen_US
dc.titleEnhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activationen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalProceedings of the National Academy of Sciencesen_US
dash.depositing.authorLiu, Xiaole (Shirley) Shirley
dc.date.available2018-01-08T16:54:03Z
dc.identifier.doi10.1073/pnas.1324151111*
workflow.legacycommentsaa.no From Waiver Table Liu emailed for aa 04-24-2017 MMen_US
dash.authorsorderedfalse
dash.contributor.affiliatedHsieh, Chen-Lin
dash.contributor.affiliatedChen, Yiwen
dash.contributor.affiliatedFei, Teng
dash.contributor.affiliatedSweeney, Christopher
dash.contributor.affiliatedLee, Gwo-Shu Mary
dash.contributor.affiliatedWang, Xiaodong
dash.contributor.affiliatedGao, Yanfei
dash.contributor.affiliatedKantoff, Philip
dash.contributor.affiliatedBrown, Myles
dash.contributor.affiliatedLiu, Xiaole
dash.contributor.affiliatedBalk, Steven


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