Sp1-mediated transcriptional activation is repressed by Sp3.

Abstract

Sp1, Sp3 (SPR‐2) and Sp4 (SPR‐1) are human sequence‐specific DNA binding proteins with very similar structural features. In this report, we have analyzed Sp3 in direct comparison with Sp1. We have raised antibodies against both Sp1 and Sp3, and show that Sp3 protein, like Sp1, is expressed in various cell lines. Co‐transfection experiments in different mammalian cell lines reveal that in contrast to Sp1 and Sp4, Sp3 is not able to activate several Sp1 responsive promoters. In addition, Sp3 also fails to activate reporter constructs in Drosophila SL2 cells lacking endogenous Sp factors. Instead, we find that Sp3 represses Sp1‐mediated activation in a linear dose‐dependent manner. A mutant of Sp3 lacking the DNA binding domain does not affect activation by Sp1, suggesting that the inhibition is most likely due to the competition with Sp1 for their common binding sites. To determine if any structurally similar domain of Sp3 is able to replace partially homologous domains of Sp1, we have generated chimeric proteins and tested their activation characteristics in gene transfer experiments. It appears that neither the glutamine‐rich domains A and B nor the D domain of Sp1 can be replaced by the homologous regions of Sp3. Our results suggest that Sp3 is an inhibitory member of the Sp family.

Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression

“…Sp1 is a potent activator for a wide variety of GC-motif containing promoters, whereas Sp3 has been described as an inhibitory member of the Sp transcription factor family acting by competition with Sp1 for their common binding sites (Hagen et al, 1994;Majello et al, 1995). In contrast, for the PDGF-B gene promoter both Sp1 and Sp3 function as activators of transcription (Liang et al, 1996a,b).…”

Transcriptional regulation of the hepatocyte growth factor (HGF) gene by the Sp family of transcription factors

“…It is known that the major regulatory function of Sp1 is upregulation of its target genes. In contrast, the major function of Sp3 is down regulation (although exceptions exist; for example, the PDGF-B promoter was reported to be upregulated by Sp3 (Hagen et al, 1994;Liang et al, 1996), presumably by competing with Sp1 for the same binding site). Because Sp1 and Sp3 bind to the same DNA sequence, it is di cult to di erentiate their functions by changing the binding site.…”

Sp1 Is Required for Glucose-Induced Transcriptional Regulation of Mouse Vesicular Glutamate Transporter 2 Gene

“…Additional transcription factors (Sp2, Sp3, and Sp4), with structural and transcriptional properties similar to those of Sp1, have been cloned, and together they form a Sp1 multigene family 33 . Functional studies have shown that Sp1 and Sp4 generally act as transcriptional activators 30,34 , while Sp3 acts as both a repressor and an activator 35,36 . Deletion and mutation analysis of putative Sp1 cis-elements of mVGLUT2 suggested a potential role of Sp1 involved in the basal promoter activity.…”