Sp3 represses transcription when tethered to promoter DNA or targeted to promoter proximal RNA.

Sp3 is a member of the Sp family of transcription factors, and it binds to the GC box with an affinity and specificity comparable with that of Sp1. Previous studies have shown that Sp3 repressed Sp1-mediated transcriptional activation, suggesting that Sp3 is an inhibitory member of the Sp family. The experiments described here demonstrate that Sp3 contains a portable repression domain that can function independently from the zinc finger DNA-binding domain. We found that the amino-terminal region of Sp3 tethered to a promoter DNA by connecting to a heterologous DNA-binding protein domain represses transcriptional activation by different positive regulators. Moreover, we determined that Sp3 targeted to a promoter-proximal RNA sequence acts as a transcriptional repressor. Taken together, our results suggest that Sp3 functions as a repressor by protein-protein interaction with components of the general transcription complex.