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dc.contributor.authorWilson, S.
dc.contributor.authorFan, L.
dc.contributor.authorSahgal, N.
dc.date.accessioned2019-11-01T12:49:39Z
dc.date.available2019-11-01T12:49:39Z
dc.date.issued2017
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85016907107&doi=10.18632%2foncotarget.15681&partnerID=40&md5=4b73968caac0b911f24372ebdfdcb0ae
dc.identifier.urihttp://hdl.handle.net/10713/11345
dc.description.abstractThe lysine demethylase 3A (KDM3A, JMJD1A or JHDM2A) controls transcriptional networks in a variety of biological processes such as spermatogenesis, metabolism, stem cell activity, and tumor progression. We matched transcriptomic and ChIPSeq profiles to decipher a genome-wide regulatory network of epigenetic control by KDM3A in prostate cancer cells. ChIP-Seq experiments monitoring histone 3 lysine 9 (H3K9) methylation marks show global histone demethylation effects of KDM3A. Combined assessment of histone demethylation events and gene expression changes presented major transcriptional activation suggesting that distinct oncogenic regulators may synergize with the epigenetic patterns by KDM3A. Pathway enrichment analysis of cells with KDM3A knockdown prioritized androgen signaling indicating that KDM3A plays a key role in regulating androgen receptor activity. Matched ChIPSeq and knockdown experiments of KDM3A in combination with ChIP-Seq of the androgen receptor resulted in a gain of H3K9 methylation marks around androgen receptor binding sites of selected transcriptional targets in androgen signaling including positive regulation of KRT19, NKX3-1, KLK3, NDRG1, MAF, CREB3L4, MYC, INPP4B, PTK2B, MAPK1, MAP2K1, IGF1, E2F1, HSP90AA1, HIF1A, and ACSL3. The cancer systems biology analysis of KDM3A-dependent genes identifies an epigenetic and transcriptional network in androgen response, hypoxia, glycolysis, and lipid metabolism. Genome-wide ChIP-Seq data highlights specific gene targets and the ability of epigenetic master regulators to control oncogenic pathways and cancer progression.en_US
dc.description.sponsorshipF.V.F. is grateful for the support of grants CA154887 and CA176114 from the National Institutes of Health, National Cancer Institute. J.Q. is supported by grants CA154888 and CA207118 from the National Institutes of Health, National Cancer Institute. This work is supported by UC CRCC CRN-17-427258, GCR, and HSRI program grants.en_US
dc.description.urihttps://doi.org/10.18632/oncotarget.15681en_US
dc.language.isoen_USen_US
dc.publisherImpact Journals LLCen_US
dc.relation.ispartofOncotarget
dc.subjectCancer systems biologyen_US
dc.subjectChIP-Seqen_US
dc.subjectEpigenomicsen_US
dc.subjectOncogeneen_US
dc.subjectProstate canceren_US
dc.titleThe histone demethylase KDM3A regulates the transcriptional program of the androgen receptor in prostate cancer cellsen_US
dc.typeArticleen_US
dc.identifier.doi10.18632/oncotarget.15681


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