Show simple item record

dc.contributor.authorRamanand, SG
dc.contributor.authorChen, Y
dc.contributor.authorYuan, J
dc.contributor.authorDaescu, K
dc.contributor.authorLambros, MB
dc.contributor.authorHoulahan, KE
dc.contributor.authorCarreira, S
dc.contributor.authorYuan, W
dc.contributor.authorBaek, G
dc.contributor.authorSharp, A
dc.contributor.authorPaschalis, A
dc.contributor.authorKanchwala, M
dc.contributor.authorGao, Y
dc.contributor.authorAslam, A
dc.contributor.authorSafdar, N
dc.contributor.authorZhan, X
dc.contributor.authorRaj, GV
dc.contributor.authorXing, C
dc.contributor.authorBoutros, PC
dc.contributor.authorde Bono, J
dc.contributor.authorZhang, MQ
dc.contributor.authorMani, RS
dc.date.accessioned2020-08-26T13:24:03Z
dc.date.issued2020-08
dc.identifier.citationThe Journal of clinical investigation, 2020, 130 (8), pp. 3987 - 4005
dc.identifier.issn0021-9738
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4013
dc.identifier.eissn1558-8238
dc.identifier.doi10.1172/jci134260
dc.description.abstractTranscriptional dysregulation is a hallmark of prostate cancer (PCa). We mapped the RNA polymerase II-associated (RNA Pol II-associated) chromatin interactions in normal prostate cells and PCa cells. We discovered thousands of enhancer-promoter, enhancer-enhancer, as well as promoter-promoter chromatin interactions. These transcriptional hubs operate within the framework set by structural proteins - CTCF and cohesins - and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1. By combining analyses from metastatic castration-resistant PCa (mCRPC) specimens, we show that AR locus amplification contributes to the transcriptional upregulation of the AR gene by increasing the total number of chromatin interaction modules comprising the AR gene and its distal enhancer. We deconvoluted the transcription control modules of several PCa genes, notably the biomarker KLK3, lineage-restricted genes (KRT8, KRT18, HOXB13, FOXA1, ZBTB16), the drug target EZH2, and the oncogene MYC. By integrating clinical PCa data, we defined a germline-somatic interplay between the PCa risk allele rs684232 and the somatically acquired TMPRSS2-ERG gene fusion in the transcriptional regulation of multiple target genes - VPS53, FAM57A, and GEMIN4. Our studies implicate changes in genome organization as a critical determinant of aberrant transcriptional regulation in PCa.
dc.formatPrint
dc.format.extent3987 - 4005
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.titleThe landscape of RNA polymerase II-associated chromatin interactions in prostate cancer.
dc.typeJournal Article
dcterms.dateAccepted2020-04-23
rioxxterms.versionofrecord10.1172/jci134260
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfThe Journal of clinical investigation
pubs.issue8
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/17/18 Starting Cohort
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/17/18 Starting Cohort
pubs.publication-statusPublished
pubs.volume130
pubs.embargo.termsNot known
icr.researchteamCancer Biomarkersen_US
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
icr.researchteamTranslational Therapeuticsen_US
dc.contributor.icrauthorPaschalis, Alecen
dc.contributor.icrauthorSharp, Adamen
dc.contributor.icrauthorCarreira, Suzanneen
dc.contributor.icrauthorDe Bono, Johannen


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record