2 REPRESSOR ELEMENTS INHIBIT EXPRESSION OF THE VON-WILLEBRAND-FACTOR GENE PROMOTER IN-VITRO

A fragment of the human von Willebrand factor (VWF) gene promoter corr esponding to sequences -487 to +247 bp functions as an endothelial spe cific promoter in cell culture. We have previously reported that a GAT A transcription Factor functions as an activator and an NF1 like prote in functions as a repressor of this promoter fragment. We have now ide ntified a second negative regulatory element in the VWF promoter that interacts with nuclear factor(s) (designated R) in both bovine aortic endothelial and smooth muscle cells. Inhibition of either the NF1 or t he R repressor alone is not sufficient to activate the VWF promoter in smooth muscle cells. The present studies reveal that simultaneous inh ibition of both repressors activates the VWF promoter in smooth muscle cells. The data support a model of selective derepression to explain the endothelial cell specific activity of the -487 to +247 fragment of the VWF promoter in vitro.