dc.contributor.author | Liu, NQ | |
dc.contributor.author | Ter Huurne, M | |
dc.contributor.author | Nguyen, LN | |
dc.contributor.author | Peng, T | |
dc.contributor.author | Wang, S-Y | |
dc.contributor.author | Studd, JB | |
dc.contributor.author | Joshi, O | |
dc.contributor.author | Ongen, H | |
dc.contributor.author | Bramsen, JB | |
dc.contributor.author | Yan, J | |
dc.contributor.author | Andersen, CL | |
dc.contributor.author | Taipale, J | |
dc.contributor.author | Dermitzakis, ET | |
dc.contributor.author | Houlston, RS | |
dc.contributor.author | Hubner, NC | |
dc.contributor.author | Stunnenberg, HG | |
dc.date.accessioned | 2017-03-24T15:08:06Z | |
dc.date.issued | 2017-02-14 | |
dc.identifier.citation | Nature communications, 2017, 8 pp. 14418 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/523 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/ncomms14418 | |
dc.description.abstract | Genome-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.format | Electronic | |
dc.format.extent | 14418 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Humans | |
dc.subject | Colorectal Neoplasms | |
dc.subject | Colonic Neoplasms | |
dc.subject | Disease Progression | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Protein-Serine-Threonine Kinases | |
dc.subject | Intracellular Signaling Peptides and Proteins | |
dc.subject | DNA-Binding Proteins | |
dc.subject | Proteome | |
dc.subject | Transcription Factors | |
dc.subject | Proteomics | |
dc.subject | DNA Methylation | |
dc.subject | Epigenesis, Genetic | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Alleles | |
dc.subject | Promoter Regions, Genetic | |
dc.subject | Genome-Wide Association Study | |
dc.subject | CRISPR-Cas Systems | |
dc.subject | MutL Protein Homolog 1 | |
dc.title | The non-coding variant rs1800734 enhances DCLK3 expression through long-range interaction and promotes colorectal cancer progression. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-12-28 | |
rioxxterms.versionofrecord | 10.1038/ncomms14418 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-02-14 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.notes | No 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-status | Published | |
pubs.volume | 8 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Cancer Genomics | |
dc.contributor.icrauthor | Studd, James | |
dc.contributor.icrauthor | Houlston, Richard | |