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Gene Review

Sp1  -  trans-acting transcription factor 1

Mus musculus

Synonyms: 1110003E12Rik, AA450830, AI845540, Sp1-1, Transcription factor Sp1
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Disease relevance of Sp1

  • Two mutant Rb promoter-LacZ constructs were used to evaluate the importance of a single E2F site or a nearby activator (Sp1/Ets) site that is found mutated in low-penetrance retinoblastomas [1].
  • Furthermore, the probe contains the Sp1 consensus binding sequence 5'CCGCCC3', in addition to the MRE consensus sequence, 5'TGCAC3', and we show that a Simian Virus 40 DNA fragment which contains six Sp1 binding sites did not bind p108 nor did it compete for the protein(s) interacting with MREd in a DNA footprinting assay [2].
  • Surprisingly, vehicle-treated -/- mice displayed fibrosis and increased Sp1, skeletal actin, Nkx2.5, and GATA-4 expression without hypertrophy [3].
  • Using a fragment spanning the region from nt -174 to +70 of the Ahr promoter, we found that four regions corresponding to four Sp1 sites were protected from DNase I digestion using nuclear extracts from MLE-12 (lung), F9 (embryonal carcinoma), Hepa-1 (hepatoma), and 41-5a (epidermal) cells [4].
  • Analysis of restriction fragment length polymorphisms in recombinant inbred, congenic, and interspecific backcross mice using human and mouse cDNA probes demonstrated that Sp1-1 is a single gene closely linked to the mammary tumor virus integration site-1 (Int-1) on the distal end of chromosome 15 [5].

Psychiatry related information on Sp1


High impact information on Sp1

  • We demonstrate that both gene-specific activator protein Sp1 and selective components of the core transcription apparatus, including TFIID and TFIIF, are direct targets inhibited by mutant htt in a polyglutamine-dependent manner [7].
  • However, the expression of the methyl-CpG-binding protein MeCP2 is greatly reduced in Sp1-/- embryos [8].
  • In Sp1-/- embryos, the expression of many putative target genes, including cell cycle-regulated genes, is not affected, CpG islands remain methylation free, and active chromatin is formed at the globin loci [8].
  • Moreover, it has been suggested that Sp1 is linked to the maintenance of methylation-free CpG islands, the cell cycle, and the formation of active chromatin structures [8].
  • Sp1-/- embryos are retarded in development, show a broad range of abnormalities, and die around day 11 of gestation [8].

Chemical compound and disease context of Sp1


Biological context of Sp1

  • Instead, it repressed Sp1-mediated transcriptional activation, suggesting that it is an inhibitory member of this family of regulatory factors [14].
  • We found that the central region of c-Myc interacts with the zinc finger domain of Sp1 [15].
  • Transcriptional regulation of the murine acetyl-CoA synthetase 1 gene through multiple clustered binding sites for sterol regulatory element-binding proteins and a single neighboring site for Sp1 [16].
  • Analysis of the transcriptional activity of fragments of the SERCA3 promoter showed the existence of a minimal promoter region located between bases -97 and +153 that contains one ETS-binding site (EBS) and two Sp1 elements that are essential for basal transcription [17].
  • Interestingly, EGR-1 is shown to down-regulate the transcription of its own gene expression, whereas Sp1 activated Egr-1 gene expression [18].

Anatomical context of Sp1

  • To provide a genetic correlation for Sp1 activity in this system, a cell line homozygous for a targeted truncation of the Sp1 gene was derived and examined [19].
  • In corroboration, efficient promoter activity was restored in differentiated muscle cells by exogenous expression of Sp1 and Sp3 [20].
  • Basal transcription of the mouse sarco(endo)plasmic reticulum Ca2+-ATPase type 3 gene in endothelial cells is controlled by Ets-1 and Sp1 [17].
  • Endogenous Sp1 and Sp3 proteins were detected only in myoblasts and not in myotubes, which indicates that the lack of these factors causes down-regulation of the Dp71 promoter activity in differentiated cells [20].
  • EMSA analyses of a composite Egr/NF-AT site showed recruitment of Sp1 to this site in Th2 cells, but not in Th1 cells [21].

Associations of Sp1 with chemical compounds

  • Coimmunoprecipitation and glutathione S-transferase pull-down experiments demonstrate that c-Myc may form complexes with Sp1/Sp3 [15].
  • Moreover, the ability of estradiol to reverse TGF-beta1-stimulated type IV collagen synthesis is mediated by down-regulating CK2 activity, which ultimately limits the availability of unbound Sp1 to activate gene transcription [22].
  • We identified a promoter region where cooperation between Ap1 and Sp1 elements was essential for TSA-induced cx43 transcription [23].
  • We previously showed, using P19 cells as a model system, that the lamin A/C promoter has a retinoic acid-responsive element (L-RARE), and that Sp1 and Sp3 bind the CACCC box of the L-RARE [24].
  • Parthenolide and mithramycin A, inhibitors of NF-kappaB and Sp1, respectively, abolished CML-induced MCP-1 gene expression in a dose-dependent manner [25].

Physical interactions of Sp1


Enzymatic interactions of Sp1


Regulatory relationships of Sp1


Other interactions of Sp1

  • Antibody "supershift" studies demonstrated that members of the Sp (Sp1, Sp3) and nuclear hormone receptor [chicken ovalbumin upstream promoter transcription factor (COUP-TF)/erbA-related protein 3] families interact with the pressure overload-responsive unit [31].
  • This region contains multiple Sp1-binding sites and a potential initiator element, but no canonical Myc DNA-binding sites [15].
  • Furthermore, transactivation of the -97/+301 promoter fragment by Ets-1 requires the presence of both the EBS and Sp1 sites, suggesting an interaction of the transcription factors on the gene promoter [17].
  • Activation of CTP:phosphocholine cytidylyltransferase alpha expression during the S phase of the cell cycle is mediated by the transcription factor Sp1 [27].
  • Sequencing of the 5'-flanking region also revealed potential cis-acting elements for multiple transcriptional regulatory factors including Sp1, zif268, Ets, CREB, and PuF sites [32].

Analytical, diagnostic and therapeutic context of Sp1


  1. Visualizing dynamic E2F-mediated repression in vivo. Agromayor, M., Wloga, E., Naglieri, B., Abrashkin, J., Verma, K., Yamasaki, L. Mol. Cell. Biol. (2006) [Pubmed]
  2. Detection of a nuclear protein that interacts with a metal regulatory element of the mouse metallothionein 1 gene. Séguin, C., Prévost, J. Nucleic Acids Res. (1988) [Pubmed]
  3. Altered molecular response to adrenoreceptor-induced cardiac hypertrophy in Egr-1-deficient mice. Saadane, N., Alpert, L., Chalifour, L.E. Am. J. Physiol. Heart Circ. Physiol. (2000) [Pubmed]
  4. Regulation of mouse Ah receptor (Ahr) gene basal expression by members of the Sp family of transcription factors. Fitzgerald, C.T., Nebert, D.W., Puga, A. DNA Cell Biol. (1998) [Pubmed]
  5. Localization of the gene for the trans-acting transcription factor Sp1 to the distal end of mouse chromosome 15. Saffer, J.D., Thurston, S.J., Annarella, M.B., Compton, J.G. Genomics (1990) [Pubmed]
  6. Decreased association of the transcription factor Sp1 with genes downregulated in Huntington's disease. Chen-Plotkin, A.S., Sadri-Vakili, G., Yohrling, G.J., Braveman, M.W., Benn, C.L., Glajch, K.E., Dirocco, D.P., Farrell, L.A., Krainc, D., Gines, S., Macdonald, M.E., Cha, J.H. Neurobiol. Dis. (2006) [Pubmed]
  7. In vitro analysis of huntingtin-mediated transcriptional repression reveals multiple transcription factor targets. Zhai, W., Jeong, H., Cui, L., Krainc, D., Tjian, R. Cell (2005) [Pubmed]
  8. Transcription factor Sp1 is essential for early embryonic development but dispensable for cell growth and differentiation. Marin, M., Karis, A., Visser, P., Grosveld, F., Philipsen, S. Cell (1997) [Pubmed]
  9. Tolfenamic acid and pancreatic cancer growth, angiogenesis, and Sp protein degradation. Abdelrahim, M., Baker, C.H., Abbruzzese, J.L., Safe, S. J. Natl. Cancer Inst. (2006) [Pubmed]
  10. The NF-kappa B and Sp1 motifs of the human immunodeficiency virus type 1 long terminal repeat function as novel thyroid hormone response elements. Desai-Yajnik, V., Samuels, H.H. Mol. Cell. Biol. (1993) [Pubmed]
  11. Involvement of Ets, rel and Sp1-like proteins in lipopolysaccharide-mediated activation of the HIV-1 LTR in macrophages. Sweet, M.J., Stacey, K.J., Ross, I.L., Ostrowski, M.C., Hume, D.A. J. Inflamm. (1998) [Pubmed]
  12. Mouse integrin alphav promoter is regulated by transcriptional factors Ets and Sp1 in melanoma cells. Tajima, A., Miyamoto, Y., Kadowaki, H., Hayashi, M. Biochim. Biophys. Acta (2000) [Pubmed]
  13. Celecoxib inhibits vascular endothelial growth factor expression in and reduces angiogenesis and metastasis of human pancreatic cancer via suppression of Sp1 transcription factor activity. Wei, D., Wang, L., He, Y., Xiong, H.Q., Abbruzzese, J.L., Xie, K. Cancer Res. (2004) [Pubmed]
  14. An inhibitor domain in Sp3 regulates its glutamine-rich activation domains. Dennig, J., Beato, M., Suske, G. EMBO J. (1996) [Pubmed]
  15. Myc represses the p21(WAF1/CIP1) promoter and interacts with Sp1/Sp3. Gartel, A.L., Ye, X., Goufman, E., Shianov, P., Hay, N., Najmabadi, F., Tyner, A.L. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  16. Transcriptional regulation of the murine acetyl-CoA synthetase 1 gene through multiple clustered binding sites for sterol regulatory element-binding proteins and a single neighboring site for Sp1. Ikeda, Y., Yamamoto, J., Okamura, M., Fujino, T., Takahashi, S., Takeuchi, K., Osborne, T.F., Yamamoto, T.T., Ito, S., Sakai, J. J. Biol. Chem. (2001) [Pubmed]
  17. Basal transcription of the mouse sarco(endo)plasmic reticulum Ca2+-ATPase type 3 gene in endothelial cells is controlled by Ets-1 and Sp1. Hadri, L., Ozog, A., Soncin, F., Lompré, A.M. J. Biol. Chem. (2002) [Pubmed]
  18. Detection and characterization of cellular EGR-1 binding to its recognition site. Cao, X., Mahendran, R., Guy, G.R., Tan, Y.H. J. Biol. Chem. (1993) [Pubmed]
  19. Sp1 binding is critical for promoter assembly and activation of the MCP-1 gene by tumor necrosis factor. Ping, D., Boekhoudt, G., Zhang, F., Morris, A., Philipsen, S., Warren, S.T., Boss, J.M. J. Biol. Chem. (2000) [Pubmed]
  20. Dystrophin Dp71 expression is down-regulated during myogenesis: role of Sp1 and Sp3 on the Dp71 promoter activity. de León, M.B., Montañez, C., Gómez, P., Morales-Lázaro, S.L., Tapia-Ramírez, V., Valadez-Graham, V., Recillas-Targa, F., Yaffe, D., Nudel, U., Cisneros, B. J. Biol. Chem. (2005) [Pubmed]
  21. Differential expression of Fas ligand in Th1 and Th2 cells is regulated by early growth response gene and NF-AT family members. Dzialo-Hatton, R., Milbrandt, J., Hockett, R.D., Weaver, C.T. J. Immunol. (2001) [Pubmed]
  22. Protein kinase CK2 mediates TGF-beta1-stimulated type IV collagen gene transcription and its reversal by estradiol. Zdunek, M., Silbiger, S., Lei, J., Neugarten, J. Kidney Int. (2001) [Pubmed]
  23. A histone deacetylation-dependent mechanism for transcriptional repression of the gap junction gene cx43 in prostate cancer cells. Hernandez, M., Shao, Q., Yang, X.J., Luh, S.P., Kandouz, M., Batist, G., Laird, D.W., Alaoui-Jamali, M.A. Prostate (2006) [Pubmed]
  24. c-Jun and Sp1 family are critical for retinoic acid induction of the lamin A/C retinoic acid-responsive element. Okumura, K., Hosoe, Y., Nakajima, N. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  25. Role of receptor for advanced glycation end-products and signalling events in advanced glycation end-product-induced monocyte chemoattractant protein-1 expression in differentiated mouse podocytes. Gu, L., Hagiwara, S., Fan, Q., Tanimoto, M., Kobata, M., Yamashita, M., Nishitani, T., Gohda, T., Ni, Z., Qian, J., Horikoshi, S., Tomino, Y. Nephrol. Dial. Transplant. (2006) [Pubmed]
  26. Communication between NF-kappa B and Sp1 controls histone acetylation within the proximal promoter of the monocyte chemoattractant protein 1 gene. Boekhoudt, G.H., Guo, Z., Beresford, G.W., Boss, J.M. J. Immunol. (2003) [Pubmed]
  27. Activation of CTP:phosphocholine cytidylyltransferase alpha expression during the S phase of the cell cycle is mediated by the transcription factor Sp1. Banchio, C., Schang, L.M., Vance, D.E. J. Biol. Chem. (2003) [Pubmed]
  28. Sp1 site is crucial for the mouse claudin-19 gene expression in the kidney cells. Luk, J.M., Tong, M.K., Mok, B.W., Tam, P.C., Yeung, W.S., Lee, K.F. FEBS Lett. (2004) [Pubmed]
  29. Phosphorylation of Sp1 by cyclin-dependent kinase 2 modulates the role of Sp1 in CTP:phosphocholine cytidylyltransferase alpha regulation during the S phase of the cell cycle. Banchio, C., Schang, L.M., Vance, D.E. J. Biol. Chem. (2004) [Pubmed]
  30. Functional significance of Sp1, Sp2, and Sp3 transcription factors in regulation of the murine CTP:phosphocholine cytidylyltransferase alpha promoter. Bakovic, M., Waite, K.A., Vance, D.E. J. Lipid Res. (2000) [Pubmed]
  31. A role for Sp and nuclear receptor transcription factors in a cardiac hypertrophic growth program. Sack, M.N., Disch, D.L., Rockman, H.A., Kelly, D.P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  32. The mouse extracellular signal-regulated kinase 2 gene. Gene structure and characterization of the promoter. Sugiura, N., Suga, T., Ozeki, Y., Mamiya, G., Takishima, K. J. Biol. Chem. (1997) [Pubmed]
  33. Regulation of the transglutaminase I gene. Identification of DNA elements involved in its transcriptional control in tracheobronchial epithelial cells. Medvedev, A., Saunders, N.A., Matsuura, H., Chistokhina, A., Jetten, A.M. J. Biol. Chem. (1999) [Pubmed]
  34. HER-2/neu represses the metastasis suppressor RECK via ERK and Sp transcription factors to promote cell invasion. Hsu, M.C., Chang, H.C., Hung, W.C. J. Biol. Chem. (2006) [Pubmed]
  35. Transforming growth factor-beta up-regulates the beta 5 integrin subunit expression via Sp1 and Smad signaling. Lai, C.F., Feng, X., Nishimura, R., Teitelbaum, S.L., Avioli, L.V., Ross, F.P., Cheng, S.L. J. Biol. Chem. (2000) [Pubmed]
  36. Transcription factor Sp1 activates involucrin promoter activity in non-epithelial cell types. Banks, E.B., Crish, J.F., Eckert, R.L. Biochem. J. (1999) [Pubmed]
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