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dc.contributor.authorKuosmanen, Suvi M
dc.contributor.authorViitala, Sari
dc.contributor.authorLaitinen, Tuomo
dc.contributor.authorPeräkylä, Mikael
dc.contributor.authorPölönen, Petri
dc.contributor.authorKansanen, Emilia
dc.contributor.authorLeinonen, Hanna
dc.contributor.authorRaju, Suresh
dc.contributor.authorWienecke-Baldacchino, Anke
dc.contributor.authorNärvänen, Ale
dc.contributor.authorPoso, Antti
dc.contributor.authorHeinäniemi, Merja
dc.contributor.authorHeikkinen, Sami
dc.contributor.authorLevonen, Anna-Liisa
dc.date.accessioned2016-10-12T10:32:10Z
dc.date.available2016-10-12T10:32:10Z
dc.date.issued2016
dc.identifier10.1093/nar/gkw052fi_FI
dc.identifier.citationKuosmanen, S. M., Viitala, S., Laitinen, T., Peräkylä, M., Pölönen, P., Kansanen, E., … Levonen, A.-L. (2016). The Effects of Sequence Variation on Genome-wide NRF2 Binding—New Target Genes and Regulatory SNPs. Nucleic Acids Research, 44(4), 1760–1775. http://doi.org/10.1093/nar/gkw052fi_FI
dc.identifier.issn0305-1048
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/156
dc.descriptionArticle
dc.description.abstractTranscription factor binding specificity is crucial for proper target gene regulation. Motif discovery algorithms identify the main features of the binding patterns, but the accuracy on the lower affinity sites is often poor. Nuclear factor E2-related factor 2 (NRF2) is a ubiquitous redox-activated transcription factor having a key protective role against endogenous and exogenous oxidant and electrophile stress. Herein, we decipher the effects of sequence variation on the DNA binding sequence of NRF2, in order to identify both genome-wide binding sites for NRF2 and disease-associated regulatory SNPs (rSNPs) with drastic effects on NRF2 binding. Interactions between NRF2 and DNA were studied using molecular modelling, and NRF2 chromatin immunoprecipitation-sequence datasets together with protein binding microarray measurements were utilized to study binding sequence variation in detail. The binding model thus generated was used to identify genome-wide binding sites for NRF2, and genomic binding sites with rSNPs that have strong effects on NRF2 binding and reside on active regulatory elements in human cells. As a proof of concept, miR-126–3p and -5p were identified as NRF2 target microRNAs, and a rSNP (rs113067944) residing on NRF2 target gene (Ferritin, light polypeptide, FTL) promoter was experimentally verified to decrease NRF2 binding and result in decreased transcriptional activity.fi_FI
dc.language.isoENfi_FI
dc.publisherOxford University Pressfi_FI
dc.relation.ispartofseriesNUCLEIC ACIDS RESEARC
dc.relation.urihttp://doi.org/10.1093/nar/gkw052fi_FI
dc.rightsCC BY-NC https://creativecommons.org/licenses/by-nc/4.0/fi_FI
dc.titleThe Effects of Sequence Variation on Genome-wide NRF2 Binding - New Target Genes and Regulatory SNPsfi_FI
dc.typehttp://purl.org/eprint/type/JournalArticle
dc.description.versionPublisher's pdffi_FI
dc.contributor.departmentFaculty of Health Sciences
dc.contributor.departmentA.I. Virtanen Institute / Biotechnology and Molecular Medicine
dc.contributor.departmentA.I. Virtanen Institute / Neurobiology,School of Medicine / Biomedicine,School of Pharmacy, Activities
uef.solecris.id41350144
eprint.statushttp://purl.org/eprint/status/PeerReviewedfi_FI
dc.type.publicationinfo:eu-repo/semantics/article
dc.rights.accessrights© Authors
dc.relation.doi10.1093/nar/gkw052
dc.description.reviewstatushttp://purl.org/eprint/status/PeerReviewed
dc.format.pagerange1760-1775
dc.relation.issn0305-1048
dc.relation.issue4
dc.relation.volume44


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