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dc.contributor.authorToropainen Sari
dc.contributor.authorNiskanen Einari A
dc.contributor.authorMalinen Marjo
dc.contributor.authorSutinen Päivi
dc.contributor.authorKaikkonen Minna U
dc.contributor.authorPalvimo Jorma J
dc.date.accessioned2017-02-23T11:55:37Z
dc.date.available2017-02-23T11:55:37Z
dc.date.issued2016
dc.identifier10.1038/srep33510fi_FI
dc.identifier.issn2045-2322
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/361
dc.descriptionArticle
dc.description.abstractAndrogen receptor (AR) is a male sex steroid-activated transcription factor (TF) that plays a critical role in prostate cancers, including castration-resistant prostate cancers (CRPC) that typically express amplified levels of the AR. CRPC-derived VCaP cells display an excessive number of chromatin AR-binding sites (ARBs) most of which localize to distal inter- or intragenic regions. Here, we analyzed direct transcription programs of the AR in VCaP cells using global nuclear run-on sequencing (GRO-seq) and integrated the GRO-seq data with the ARB and VCaP cell-specific TF-binding data. Androgen immediately activated transcription of hundreds of protein-coding genes, including IGF-1 receptor and EGF receptor. Androgen also simultaneously repressed transcription of a large number of genes, including MYC. As functional enhancers have been postulated to produce enhancer-templated non-coding RNAs (eRNAs), we also analyzed the eRNAs, which revealed that only a fraction of the ARBs reside at functional enhancers. Activation of these enhancers was most pronounced at the sites that also bound PIAS1, ERG and HDAC3, whereas binding of HDAC3 and PIAS1 decreased at androgen-repressed enhancers. In summary, our genome-wide data of androgen-regulated enhancers and primary target genes provide new insights how the AR can directly regulate cellular growth and control signaling pathways in CPRC cellsfi_FI
dc.language.isoENfi_FI
dc.publisherNature Publishing Groupfi_FI
dc.relation.ispartofseriesScientific Reports
dc.relation.urihttp://doi.org/10.1038/srep33510fi_FI
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/fi_FI
dc.subjectProstate cancerfi_FI
dc.subjectTranscriptional regulatory elementsfi_FI
dc.titleGlobal analysis of transcription in castration-resistant prostate cancer cells uncovers active enhancers and direct androgen receptor targetsfi_FI
dc.typehttp://purl.org/eprint/type/JournalArticle
dc.description.versionPublisher's pdffi_FI
dc.contributor.departmentSchool of Medicine / Biomedicine
dc.contributor.departmentA.I. Virtanen -instituutti / Bioteknologia ja molekulaarinen lääketiede
uef.solecris.id42681717
eprint.statushttp://purl.org/eprint/status/PeerReviewedfi_FI
dc.type.publicationinfo:eu-repo/semantics/article
dc.rights.accessrights© Authorsfi_FI
uef.citationinfo.issue6
uef.citationinfo.pages33510
dc.relation.doi10.1038/srep33510
dc.description.reviewstatushttp://purl.org/eprint/status/PeerReviewed
dc.relation.articlenumber33510
dc.relation.issn2045-2322
dc.relation.issue6


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