Reference : The Effects of Sequence Variation on Genome-wide NRF2 Binding––New Target Genes and R...
Scientific journals : Article
Life sciences : Multidisciplinary, general & others
http://hdl.handle.net/10993/26354
The Effects of Sequence Variation on Genome-wide NRF2 Binding––New Target Genes and Regulatory SNPs
English
Kuosmanen, Suvi [A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland > Department of Biotechnology and Molecular Medicine]
Viitala, Sari [University of Eastern Finland > School of Pharmacy]
Laitinen, Tuomo [University of Eastern Finland > School of Pharmacy]
Peräkylä, Mikael [University of Eastern Finland > School of Pharmacy]
Pölönen, Petri [A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland > Department of Biotechnology and Molecular Medicine > > ; Institute of Biomedicine, School of Medicine, University of Eastern Finland]
Kansanen, Emilia [A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland > Department of Biotechnology and Molecular Medicine]
Leinonen, Hanna [A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland > Department of Biotechnology and Molecular Medicine]
Raju, Suresh [Institute of Biomedicine, School of Medicine, University of Eastern Finland]
Wienecke, Anke mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > > ; Luxembourg Institute of Health]
Närvänen, Ale [University of Eastern Finland > School of Pharmacy]
Poso, Antti [University of Eastern Finland > School of Pharmacy]
Heinäniemi, Merja [Institute of Biomedicine, School of Medicine, University of Eastern Finland]
Heikkinen, Sami [Institute of Biomedicine, School of Medicine, University of Eastern Finland]
Levonen, Anna-Liisa [A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland > Department of Biotechnology and Molecular Medicine]
Jan-2016
Nucleic Acids Research
Oxford University Press
44
4
1760-1775
Yes (verified by ORBilu)
0305-1048
1362-4962
Oxford
United Kingdom
[en] Transcription 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 bind- ing 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.
http://hdl.handle.net/10993/26354
10.1093/nar/gkw052

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