SP3 IS A BIFUNCTIONAL TRANSCRIPTION REGULATOR WITH MODULAR INDEPENDENT ACTIVATION AND REPRESSION DOMAINS

Sp3 is a member of the Sp family of transcription factors and binds to DNA with affinity and specificity comparable to that of Spl. We demon strate that Sp3 is a bifunctional transcription factor that can both a ctivate and repress transcription, Gene fusion experiments in mammalia n cells demonstrate that the Sp3 activation potential is distributed o ver an extensive glutamine-rich N-terminal region, whereas the repress or activity has been mapped in a 72-amino acid region located at the 5 ' of the zinc finger DNA-binding domain, We demonstrated that the repr ession activity is strictly dependent on the context of the DNA-bindin g sites bound by Sp3. We found that Sp3 represses transcription of pro moters bearing multiple GAL4 DNA-binding sites, whereas it activates i sogenic reporters containing a single GAL4-binding site, Transfection experiments in Drosophila cells that lack endogenous Sp activity demon strated that Sp3 does not possess an active repression domain that can function in insect cells, rather it is a weak transcriptional activat or of the c-myc promoter. Our results strongly suggest that Sp3 is a d ual-function regulator whose activity is dependent upon both the promo ter and the cellular context.