Article

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
ABSTRACT
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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    • "This suggests that Sp1 and Sp3 are important in the remodeling of chromatin and the regulation of gene expression (Li & Davie, 2010 ). Sp3 represses the Sp1-mediated trans-activation of promoters bearing two or more Sp1-binding sites, yet it does not affect the Sp1-mediated trans-activation of promoters with only one Sp1 site, and Sp3 cannot trans-activate synergistically through two or more Sp1-binding sites (Yu et al., 2003). Sp1 can be modified by phosphorylation, sumoylation, acetylation and glycosylation, while Sp3 modifications include phosphorylation, sumoylation, and acetylation. "
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    • "In this report, the impact of decline in ARSB on Sp1 in colonic epithelium has been shown using specific inhibitors of Sp1, including Sp1 siRNA and Mithramycin A. Studies to address possible contributions of other SP family members are of interest, since SP transcription factor paralogs, including Sp3 and Sp4, have co-evolved with Sp1, and competition for binding at GC box consensus sites can lead to complex regulatory interactions, particularly involving Sp1 and Sp3505152. The potential interactions between multiple transcriptionally active SP binding sites indicate that intricate, complex regulatory mechanisms are involved53545556. Distinctive properties and effects of Sp4 have also been recognized [57]. "
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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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