Stability of the Sp3-DNA complex is promoter-specific: Sp3 efficiently competes with Sp1 for binding to promoters containing multiple Sp-sites

Center for Molecular Biology of Oral Diseases, College of Dentistry (M/C 860), University of Illinois at Chicago, 801 South Paulina Street, Chicago, IL 60612, USA.
Nucleic Acids Research (Impact Factor: 9.11). 10/2003; 31(18):5368-76. DOI: 10.1093/nar/gkg706
Source: PubMed


The transcription regulatory protein Sp3 shares more than 90% sequence homology with Sp1 in the DNA-binding domain and they bind to the same cognate DNA-element. However, the transcriptional activities of these two Sp-family factors are not equivalent. While Sp1 functions strictly as a transcriptional activator, Sp3 has been shown to be transcriptionally inactive for promoters containing multiple Sp-binding sites. In the present study, we show that the DNA-binding property of Sp3 is promoter dependent and is different from Sp1. The 116 kDa Sp3 polypeptide binds as a monomer to a single Sp-binding site but readily forms slower migrating complexes with adjacent Sp-binding sites. The slower migrating Sp3-DNA complexes are significantly more stable than monomeric Sp3-DNA complexes or multimeric Sp1-DNA complexes. As a consequence, Sp3 can efficiently compete with Sp1 for binding to regions containing multiple Sp sites. The transcription regulatory function of Sp3 is also significantly different from Sp1. Unlike Sp1, Sp3 does not synergistically activate transcription of promoters containing multiple Sp-binding sites. Therefore, although Sp3 is a transcription activator, Sp3 reduces Sp1-dependent transcription of promoters containing adjacent Sp-binding sites by competing with Sp1 for promoter occupancy and thereby blocking the synergistic transactivation function of Sp1. Taken together, this study provides a possible mechanism of the promoter-specific transcription repression function of Sp3.

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    • "Interestingly, Sp1 is a known transcriptional activator [36], [37] but Sp3 can act either as a transcriptional activator or repressor [38]. For example, Sp3 can competes the GC-box binding with Sp1 resulting in negative regulation of the promoter [39]–[42]. "
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    • "In spite of extensive studies on the Sp proteins, the difference in binding properties between Sp1 and Sp3 remains largely unknown. Notably, one study shows that promoters containing multiple adjacent Sp-binding sites form significantly more stable Sp3-DNA complexes than those with single Sp-binding sites, and as a consequence, Sp3 efficiently displaces Sp1 from preformed Sp1-DNA complexes from such sites [18]. Therefore, in AFAP1L1's promoter region, the Sp3-SBS1 complexes might be more more stable than the Sp1-SBS1 complexes, because SBS1 contains two overlapping consensus Sp-binding sequences. "
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    • "Whereas Sp1 is usually an activator of transcription, Sp3 functions either as an activator or as a repressor [12] [13] [14]. Although Sp3 lacks the ability of Sp1 to bind to DNA as a multimer, it can antagonize Sp1 by blocking its synergistic transactivation function [15]. Sp1 and Sp3 generally compete for the same binding sites on a variety of promoters and regulate the target gene expression [16] [17] [18] [19] [20] [21]. "
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