DIFFERENTIAL TRANSCRIPTIONAL REGULATION OF C-MYC PROMOTER THROUGH THESAME DNA-BINDING SITES TARGETED BY SP1-LIKE PROTEINS

Sp1 and Sp3 are closely related members of a gene family encoding prot eins with very similar structural features. The zinc finger DNA bindin g domains of Sp1 and Sp3 are highly conserved and they bind to GC and GT box with comparable affinities. To begin to delineate the specific roles of these two members of the Sp1-like gene family, here we have a nalysed the DNA binding specificity and their effects on activation of human c-myc promoter. We found that both proteins bind to the same si tes of c-myc promoter, upstream to both the P1 and P2 initiation sites . Cotransfection experiments, in mammalian and insect cells, indicated that Sp1 trans-activate c-myc promoter, whereas Sp3 did not. In addit ion, enforced expression of Sp3 repressed Spl-mediated activation of c -myc. Finally, we found that Sp1 and E2F-1/DP-1 cooperatively trans-ac tivate c-myc promoter. In contrast enforced expression of Sp3 fails to repress EZF-1/DP-1-mediated activation.