A polymorphism affecting MYB binding within the promoter of the PDCD4 gene is associated with severe asthma in children.
Bottom Line: In silico analysis of PDCD4 locus showed that rs6585018:G>A had the potential to affect MYB transcription factor binding, shown to act as a PDCD4-transcription inducer.Electromobility shift assays and reporter assays revealed that rs6585018:G>A alters MYB binding thereby influencing the expression of PDCD4.Our association between a variant MYB binding site in PDCD4 and the severest form of childhood asthma therefore suggests that PDCD4 is a novel molecule of importance to asthmatic inflammatory responses.
Affiliation: Molecular Genetics and Genomics Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom. firstname.lastname@example.orgShow MeSH
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Mentions: To confirm the allele-specific effects of rs6585018:G>A polymorphism on promoter activity, two luciferase reporter constructs were generated including the MYB binding sequence 5â€² of PDCD4 and A/G at the rs6585018:G>A polymorphic site. After transient transfection into Jurkat cell lines, the relative luciferase activity of the pGL3.rs6585018+A transfected cells was found to be increased compared with pGL3.rs6585018+G transfected cells (PÂ <Â 0.02) confirming the findings from the EMSA experiments (Fig. 5).
Affiliation: Molecular Genetics and Genomics Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom. email@example.com