dc.contributor.author | Ramanand, SG | |
dc.contributor.author | Chen, Y | |
dc.contributor.author | Yuan, J | |
dc.contributor.author | Daescu, K | |
dc.contributor.author | Lambros, MB | |
dc.contributor.author | Houlahan, KE | |
dc.contributor.author | Carreira, S | |
dc.contributor.author | Yuan, W | |
dc.contributor.author | Baek, G | |
dc.contributor.author | Sharp, A | |
dc.contributor.author | Paschalis, A | |
dc.contributor.author | Kanchwala, M | |
dc.contributor.author | Gao, Y | |
dc.contributor.author | Aslam, A | |
dc.contributor.author | Safdar, N | |
dc.contributor.author | Zhan, X | |
dc.contributor.author | Raj, GV | |
dc.contributor.author | Xing, C | |
dc.contributor.author | Boutros, PC | |
dc.contributor.author | de Bono, J | |
dc.contributor.author | Zhang, MQ | |
dc.contributor.author | Mani, RS | |
dc.date.accessioned | 2020-08-26T13:24:03Z | |
dc.date.issued | 2020-08-03 | |
dc.identifier.citation | The Journal of clinical investigation, 2020, 130 (8), pp. 3987 - 4005 | |
dc.identifier.issn | 0021-9738 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4013 | |
dc.identifier.eissn | 1558-8238 | |
dc.identifier.doi | 10.1172/jci134260 | |
dc.description.abstract | Transcriptional 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.format | Print | |
dc.format.extent | 3987 - 4005 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER SOC CLINICAL INVESTIGATION INC | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.title | The landscape of RNA polymerase II-associated chromatin interactions in prostate cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-04-23 | |
rioxxterms.versionofrecord | 10.1172/jci134260 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2020-08 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | The Journal of clinical investigation | |
pubs.issue | 8 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 130 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
icr.researchteam | Translational Therapeutics | |
dc.contributor.icrauthor | Carreira, Suzanne | |
dc.contributor.icrauthor | Sharp, Adam | |
dc.contributor.icrauthor | Paschalis, Alec | |
dc.contributor.icrauthor | De Bono, Johann | |