Alternative titles; symbols
HGNC Approved Gene Symbol: SP1
Cytogenetic location: 12q13.13 Genomic coordinates (GRCh38): 12:53,380,176-53,416,446 (from NCBI)
Profound changes in patterns of gene expression can result from relatively small changes in the concentrations of sequence-specific transcription factors. Synergistic interaction between factors bound to different sites within a transcriptional control region is supported by the work of Courey et al. (1989). The transcription factor Sp1 is a DNA-binding protein which interacts with a variety of gene promoters containing GC-box elements. Kadonaga et al. (1987) cloned the human Sp1 cDNA and showed that it has contiguous zinc finger motifs and requires zinc for sequence-specific binding to DNA.
Segmentation in Drosophila is based on a cascade of hierarchical gene interactions initiated by maternally deposited morphogens that define the spatially restricted domains of gap gene expression at blastoderm. The formation of 7 head segments depends on the function of several genes. Wimmer et al. (1993) showed that one of these genes is the Drosophila homolog of the human transcription factor SP1.
Dunah et al. (2002) reported that huntingtin (HTT; 613004) interacts with the transcriptional activator SP1 and coactivator TAFII130 (601796). Coexpression of SP1 and TAFII130 in cultured striatal cells from wildtype and HD transgenic mice reverses the transcriptional inhibition of the dopamine D2 receptor gene caused by mutant huntingtin, as well as protects neurons from huntingtin-induced cellular toxicity. Furthermore, soluble mutant huntingtin inhibited SP1 binding to DNA in postmortem brain tissues of both presymptomatic and affected HD patients.
Law et al. (1998) demonstrated that ZBP89 (ZNF148; 601897) inhibited SP1 activation of the ornithine decarboxylase (ODC; 165640) gene. ZNF148 and SP1 bound to a GC box in the proximal promoter of the ODC gene in a mutually exclusive manner. Zhang et al. (2003) demonstrated that ZNF148 also repressed SP1-mediated activation of the vimentin (193060) promoter. The N-terminal zinc fingers of ZNF148 interacted with SP1 and repressed gene expression, and cotransfection of TAFII130 with ZNF148 and SP1 in insect cells rescued expression. Since both ZNF148 and TAFII130 interacted with a glutamine-rich region of SP1, Zhang et al. (2003) hypothesized that these proteins may compete for SP1 binding.
Deniaud et al. (2006) found that overexpression of human SP1 induced apoptosis in all mouse and hamster cell lines tested. The apoptotic pathways induced by SP1 overexpression were cell type specific and required the SP1 DNA-binding domain. In mouse pre-B cells, SP1-induced apoptosis was associated with downregulation of Bclxl (600039) and Bax (600040). No other Bcl2 (151430) family members, caspases (see 147678), or death receptors (see 603366) showed variation in expression following SP1 induction.
Paul et al. (2014) showed a major depletion of cystathionine gamma-lyase (CTH; 607657), the biosynthetic enzyme for cysteine, in Huntington disease (143100) tissues, which may mediate Huntington disease pathophysiology. The defect occurs at the transcriptional level and seems to reflect influences of mutant huntingtin on SP1, a transcriptional activator for CTH. Consistent with the notion of loss of CTH as a pathogenic mechanism, supplementation with cysteine reversed abnormalities in cultures of Huntington disease tissues and in intact mouse models of Huntington disease, suggesting therapeutic potential.
Szpirer et al. (1991) assigned the SP1 gene to 12q by study of somatic cell hybrids. By a similar method, they showed that the homologous gene is carried by rat chromosome 7. It is noteworthy that the vitamin D receptor (VDR; 277440), which also is a transcription factor, likewise maps to human 12q and rat chromosome 7. PAH (612349) and RARG (180190) are other genes that are on human 12q and rat 7. By fluorescence in situ hybridization, Matera and Ward (1993) mapped the SP1 gene to 12q13. By in situ hybridization, Gaynor et al. (1993) concluded that 12q13.1 is the most probable location of the SP1 gene.
Courey, A. J., Holtzman, D. A., Jackson, S. P., Tjian, R. Synergistic activation by the glutamine-rich domains of human transcription factor Sp1. Cell 59: 827-836, 1989. [PubMed: 2512012] [Full Text: https://doi.org/10.1016/0092-8674(89)90606-5]
Deniaud, E., Baguet, J., Mathieu, A.-L., Pages, G., Marvel, J., Leverrier, Y. Overexpression of Sp1 transcription factor induces apoptosis. Oncogene 25: 7096-7105, 2006. [PubMed: 16715126] [Full Text: https://doi.org/10.1038/sj.onc.1209696]
Dunah, A. W., Jeong, H., Griffin, A., Kim, Y.-M., Standaert, D. G., Hersch, S. M., Mouradian, M. M., Young, A. B., Tanese, N., Krainc, D. Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science 296: 2238-2243, 2002. [PubMed: 11988536] [Full Text: https://doi.org/10.1126/science.1072613]
Gaynor, R. B., Shieh, B.-H., Klisak, I., Sparkes, R. S., Lusis, A. J. Localization of the transcription factor SP1 gene to human chromosome 12q12-q13.2. Cytogenet. Cell Genet. 64: 210-212, 1993. [PubMed: 8404040] [Full Text: https://doi.org/10.1159/000133578]
Kadonaga, J. T., Carner, K. R., Masiarz, F. R., Tjian, R. Isolation of a cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain. Cell 51: 1079-1090, 1987. [PubMed: 3319186] [Full Text: https://doi.org/10.1016/0092-8674(87)90594-0]
Law, G. L., Itoh, H., Law, D. J., Mize, G. J., Merchant, J. L., Morris, D. R. Transcription factor ZBP-89 regulates the activity of the ornithine decarboxylase promoter. J. Biol. Chem. 273: 19955-19964, 1998. [PubMed: 9685330] [Full Text: https://doi.org/10.1074/jbc.273.32.19955]
Matera, A. G., Ward, D. C. Localization of the human Sp1 transcription factor gene to 12q13 by fluorescence in situ hybridization. Genomics 17: 793-794, 1993. [PubMed: 8244404] [Full Text: https://doi.org/10.1006/geno.1993.1413]
Paul, B. D., Sbodio, J. I., Xu, R., Vandiver, M. S., Cha, J. Y., Snowman, A. M., Snyder, S. H. Cystathionine gamma-lyase deficiency mediates neurodegeneration in Huntington's disease. Nature 509: 96-100, 2014. [PubMed: 24670645] [Full Text: https://doi.org/10.1038/nature13136]
Szpirer, J., Szpirer, C., Riviere, M., Levan, G., Marynen, P., Cassiman, J.-J., Wiese, R., DeLuca, H. F. The Sp1 transcription factor gene (SP1) and the 1,25-dihydroxyvitamin D(3) receptor gene (VDR) are colocalized on human chromosome arm 12q and rat chromosome 7. Genomics 11: 168-173, 1991. [PubMed: 1662663] [Full Text: https://doi.org/10.1016/0888-7543(91)90114-t]
Wimmer, E. A., Jackle, H., Pfeifle, C., Cohen, S. M. A Drosophila homologue of human Sp1 is a head-specific segmentation gene. Nature 366: 690-694, 1993. [PubMed: 8259212] [Full Text: https://doi.org/10.1038/366690a0]
Zhang, X., Diab, I. H., Zehner, Z. E. ZBP-89 represses vimentin gene transcription by interacting with the transcriptional activator, Sp1. Nucleic Acids Res. 31: 2900-2914, 2003. [PubMed: 12771217] [Full Text: https://doi.org/10.1093/nar/gkg380]