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dc.contributor.authorLiu, NQ
dc.contributor.authorTer Huurne, M
dc.contributor.authorNguyen, LN
dc.contributor.authorPeng, T
dc.contributor.authorWang, S-Y
dc.contributor.authorStudd, JB
dc.contributor.authorJoshi, O
dc.contributor.authorOngen, H
dc.contributor.authorBramsen, JB
dc.contributor.authorYan, J
dc.contributor.authorAndersen, CL
dc.contributor.authorTaipale, J
dc.contributor.authorDermitzakis, ET
dc.contributor.authorHoulston, RS
dc.contributor.authorHubner, NC
dc.contributor.authorStunnenberg, HG
dc.date.accessioned2017-03-24T15:08:06Z
dc.date.issued2017-02-14
dc.identifier.citationNature communications, 2017, 8 pp. 14418 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/523
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/ncomms14418
dc.description.abstractGenome-wide association studies have identified a great number of non-coding risk variants for colorectal cancer (CRC). To date, the majority of these variants have not been functionally studied. Identification of allele-specific transcription factor (TF) binding is of great importance to understand regulatory consequences of such variants. A recently developed proteome-wide analysis of disease-associated SNPs (PWAS) enables identification of TF-DNA interactions in an unbiased manner. Here we perform a large-scale PWAS study to comprehensively characterize TF-binding landscape that is associated with CRC, which identifies 731 allele-specific TF binding at 116 CRC risk loci. This screen identifies the A-allele of rs1800734 within the promoter region of MLH1 as perturbing the binding of TFAP4 and consequently increasing DCLK3 expression through a long-range interaction, which promotes cancer malignancy through enhancing expression of the genes related to epithelial-to-mesenchymal transition.
dc.formatElectronic
dc.format.extent14418 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectColorectal Neoplasms
dc.subjectColonic Neoplasms
dc.subjectDisease Progression
dc.subjectGenetic Predisposition to Disease
dc.subjectProtein-Serine-Threonine Kinases
dc.subjectIntracellular Signaling Peptides and Proteins
dc.subjectDNA-Binding Proteins
dc.subjectProteome
dc.subjectTranscription Factors
dc.subjectProteomics
dc.subjectDNA Methylation
dc.subjectEpigenesis, Genetic
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAlleles
dc.subjectPromoter Regions, Genetic
dc.subjectGenome-Wide Association Study
dc.subjectCRISPR-Cas Systems
dc.subjectMutL Protein Homolog 1
dc.titleThe non-coding variant rs1800734 enhances DCLK3 expression through long-range interaction and promotes colorectal cancer progression.
dc.typeJournal Article
dcterms.dateAccepted2016-12-28
rioxxterms.versionofrecord10.1038/ncomms14418
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-02-14
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.notesNo embargo
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/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
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/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.publication-statusPublished
pubs.volume8
pubs.embargo.termsNo embargo
icr.researchteamCancer Genomicsen_US
dc.contributor.icrauthorHoulston, Richarden
dc.contributor.icrauthorStudd, Jamesen


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