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Genomic androgen receptor-occupied regions with different functions, defined by histone acetylation, coregulators and transcriptional capacity

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dc.contributor.authorJia, L.
dc.contributor.authorBerman, B.
dc.contributor.authorJariwala, U.
dc.contributor.authorYan, X.
dc.contributor.authorCogan, J.
dc.contributor.authorWalters, A.
dc.contributor.authorChen, T.
dc.contributor.authorBuchanan, G.
dc.contributor.authorFrenkel, B.
dc.contributor.authorCoetzee, G.
dc.contributor.editorFugmann, S.D.
dc.date.issued2008
dc.description.abstractBackground The androgen receptor (AR) is a steroid-activated transcription factor that binds at specific DNA locations and plays a key role in the etiology of prostate cancer. While numerous studies have identified a clear connection between AR binding and expression of target genes for a limited number of loci, high-throughput elucidation of these sites allows for a deeper understanding of the complexities of this process. Methodology/Principal Findings We have mapped 189 AR occupied regions (ARORs) and 1,388 histone H3 acetylation (AcH3) loci to a 3% continuous stretch of human genomic DNA using chromatin immunoprecipitation (ChIP) microarray analysis. Of 62 highly reproducible ARORs, 32 (52%) were also marked by AcH3. While the number of ARORs detected in prostate cancer cells exceeded the number of nearby DHT-responsive genes, the AcH3 mark defined a subclass of ARORs much more highly associated with such genes – 12% of the genes flanking AcH3+ARORs were DHT-responsive, compared to only 1% of genes flanking AcH3−ARORs. Most ARORs contained enhancer activities as detected in luciferase reporter assays. Analysis of the AROR sequences, followed by site-directed ChIP, identified binding sites for AR transcriptional coregulators FoxA1, CEBPβ, NFI and GATA2, which had diverse effects on endogenous AR target gene expression levels in siRNA knockout experiments. Conclusions/Significance We suggest that only some ARORs function under the given physiological conditions, utilizing diverse mechanisms. This diversity points to differential regulation of gene expression by the same transcription factor related to the chromatin structure.
dc.description.statementofresponsibilityLi Jia, Benjamin P. Berman, Unnati Jariwala, Xiting Yan, Jon P. Cogan, Allison Walters, Ting Chen, Grant Buchanan, Baruch Frenkel and Gerhard A. Coetzee
dc.identifier.citationPLoS One, 2008; 3(11):1-13
dc.identifier.doi10.1371/journal.pone.0003645
dc.identifier.issn1932-6203
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/2440/54187
dc.language.isoen
dc.publisherPublic Library of Science
dc.rights© 2008 Jia et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.source.urihttps://doi.org/10.1371/journal.pone.0003645
dc.subjectCell Line, Tumor
dc.subjectChromosomes, Human, Pair 19
dc.subjectChromosomes, Human, Pair 20
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectHistones
dc.subjectReceptors, Androgen
dc.subjectTranscription Factors
dc.subjectChromatin Immunoprecipitation
dc.subjectTranscription, Genetic
dc.subjectResponse Elements
dc.subjectAcetylation
dc.subjectGenome, Human
dc.subjectModels, Biological
dc.subjectMale
dc.titleGenomic androgen receptor-occupied regions with different functions, defined by histone acetylation, coregulators and transcriptional capacity
dc.typeJournal article
pubs.publication-statusPublished

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