[HTML][HTML] Circadian clock genes cause activation of the human PAI-1 gene promoter with 4G/5G allelic preference
Increased plasminogen activator inhibitor-1 (PAI-1) activity is associated with greater risk of
myocardial infarction. PAI-1 expression is regulated by a 4G/5G promoter polymorphism.
The 4G allele is associated with higher PAI-levels and greater circadian variation. Here we
show that clock protein heterodimers BMAL/CLOCK cause greater activation (≈ 2-fold, P<
0.05) of the 4G allele. Site-directed mutagenesis studies suggest that clock genes act on two
canonical E-boxes to regulate PAI-1 promoter activity. These results identify a potential …
myocardial infarction. PAI-1 expression is regulated by a 4G/5G promoter polymorphism.
The 4G allele is associated with higher PAI-levels and greater circadian variation. Here we
show that clock protein heterodimers BMAL/CLOCK cause greater activation (≈ 2-fold, P<
0.05) of the 4G allele. Site-directed mutagenesis studies suggest that clock genes act on two
canonical E-boxes to regulate PAI-1 promoter activity. These results identify a potential …
Increased plasminogen activator inhibitor-1 (PAI-1) activity is associated with greater risk of myocardial infarction. PAI-1 expression is regulated by a 4G/5G promoter polymorphism. The 4G allele is associated with higher PAI-levels and greater circadian variation. Here we show that clock protein heterodimers BMAL/CLOCK cause greater activation (≈2-fold, P<0.05) of the 4G allele. Site-directed mutagenesis studies suggest that clock genes act on two canonical E-boxes to regulate PAI-1 promoter activity. These results identify a potential novel mechanism whereby allele-specific clock genes – mediated modulation of PAI-1 expression may contribute to circadian variation in cardiac risk.
Elsevier