An upstream activator sequence regulates the murine Pgk-1 promoter and binds multiple nuclear proteins.

The murine Pgk-1 gene is driven by a strong promoter that is regulated by a 304 bp upstream activator sequence (UAS). The activity of the UAS is high in undifferentiated embryonal carcinoma cells but declines when these cells are induced to differentiate with retinoic acid. The effect of the UAS on promoter activity is particularly striking when the activity of the Pgk-1 promoter is assayed following its integration into the genome, suggesting that it may function by regulating chromatin structure in the region of the core promoter. Three sites on the UAS bind nuclear proteins. Two of these sites bind factors present in both embryonal carcinoma cells and their differentiated derivatives whereas one site binds factors present only in differentiated cells. There appears to be both cooperation and antagonism in the binding of proteins to different sites in the UAS, suggesting that the activity of the Pgk-1 promoter is determined by the constellation of proteins assembled upstream of its transcription start site.