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dc.contributor.authorLiu, NQen_US
dc.contributor.authorTer Huurne, Men_US
dc.contributor.authorNguyen, LNen_US
dc.contributor.authorPeng, Ten_US
dc.contributor.authorWang, S-Yen_US
dc.contributor.authorStudd, JBen_US
dc.contributor.authorJoshi, Oen_US
dc.contributor.authorOngen, Hen_US
dc.contributor.authorBramsen, JBen_US
dc.contributor.authorYan, Jen_US
dc.contributor.authorAndersen, CLen_US
dc.contributor.authorTaipale, Jen_US
dc.contributor.authorDermitzakis, ETen_US
dc.contributor.authorHoulston, RSen_US
dc.contributor.authorHubner, NCen_US
dc.contributor.authorStunnenberg, HGen_US
dc.date.accessioned2017-03-24T15:08:06Z
dc.date.issued2017-02-14en_US
dc.identifier.citationNature communications, 2017, 8 pp. 14418 - ?en_US
dc.identifier.issn2041-1723en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/523
dc.identifier.eissn2041-1723en_US
dc.identifier.doi10.1038/ncomms14418en_US
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.en_US
dc.formatElectronicen_US
dc.format.extent14418 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectCell Line, Tumoren_US
dc.subjectHumansen_US
dc.subjectColorectal Neoplasmsen_US
dc.subjectColonic Neoplasmsen_US
dc.subjectDisease Progressionen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectProtein-Serine-Threonine Kinasesen_US
dc.subjectIntracellular Signaling Peptides and Proteinsen_US
dc.subjectDNA-Binding Proteinsen_US
dc.subjectProteomeen_US
dc.subjectTranscription Factorsen_US
dc.subjectProteomicsen_US
dc.subjectDNA Methylationen_US
dc.subjectEpigenesis, Geneticen_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectAllelesen_US
dc.subjectPromoter Regions, Geneticen_US
dc.subjectGenome-Wide Association Studyen_US
dc.subjectCRISPR-Cas Systemsen_US
dc.subjectMutL Protein Homolog 1en_US
dc.titleThe non-coding variant rs1800734 enhances DCLK3 expression through long-range interaction and promotes colorectal cancer progression.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-12-28en_US
rioxxterms.versionofrecord10.1038/ncomms14418en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2017-02-14en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNature communicationsen_US
pubs.notesNo embargoen_US
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/Molecular & Population Genetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics
pubs.publication-statusPublisheden_US
pubs.volume8en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamMolecular & Population Geneticsen_US
dc.contributor.icrauthorHoulston, Richarden_US
dc.contributor.icrauthorStudd, Jamesen_US


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