Functional analyses of the transcription factor Sp4 reveal properties distinct from Sp1 and Sp3.

Sp4 is a human sequence-specific DNA binding protein with structural features similar to those described for the transcription factors Sp1 and Sp3. These three proteins contain two glutamine-rich regions and a highly conserved DNA binding domain composed of three zinc fingers. Consistently, Sp1, Sp3, and Sp4 do have the same DNA binding specificities. In this report, we have embarked on a detailed analysis of the transcriptional properties of Sp4 in direct comparison to Sp1 and Sp3. Cotransfection experiments into Drosophila SL2 cells lacking endogenous Sp factors demonstrate that Sp4 is an activator protein like Sp1. However, in contrast to Sp1, Sp4 is not able to act synergistically through adjacent binding sites. The transactivation function of Sp4 resides, like that of Sp1, in the N-terminal glutamine-rich region. Sp4 can function as a target for the Sp1 activation domains in a superactivation assay, suggesting that the activation domains of Sp1 and Sp4 are functionally related. Furthermore, we show that Sp4-mediated transcriptional activation can be repressed by Sp3. Taken together, our results demonstrate that the transcription factor Sp4 exhibits specific functional properties distinct from Sp1 and Sp3.