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Gene Review

Sp1  -  CG1343 gene product from transcript CG1343-RE

Drosophila melanogaster

Synonyms: CG1343, D-Sp1, D-Sp8, D.Sp1, Dmel\CG1343, ...
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Disease relevance of Sp1


High impact information on Sp1


Biological context of Sp1

  • The requirement for btd and Sp1 persists during the development of ventral discs: inactivation by RNA interference results in a strong reduction of the size of legs and antennae [9].
  • D-Sp1 is located in the same cytological location as btd in chromosome band 9A on the X-chromosome [10].
  • Taken together, these studies indicate that transcriptional activation through the concerted action of SREBP and Sp1 can occur by at least two different mechanisms, and promoters that are activated by each one can potentially be identified by the number of critical SREBP binding sites that they contain [1].
  • While overexpression of any of several TAFs did not affect basal transcription, in either the presence or the absence of cotransfected dTBP, overexpression of TAFII230 inhibited transcriptional activation mediated by p53-GAL4 as well as by GAL4-VP16 and Sp1 [11].
  • We have detected DNA binding activity for a synthetic oligonucleotide containing an Sp1 consensus sequence in nuclear extracts from human chondrocytes [12].

Anatomical context of Sp1

  • Furthermore, BTD and Sp1 are capable of activating transcription in transfected cultured cells through interaction with the same DNA target sites [13].
  • The results suggest that D-Sp1 and btd represent a novel gene pair with partially redundant functions after the blastoderm stage [14].
  • Detection and characterization of Sp1 binding activity in human chondrocytes and its alterations during chondrocyte dedifferentiation [12].
  • Sp1 and Sp3 binding to the p21 promoter increased during Caco-2 cell differentiation, while the absolute level of Sp1 did not change and the absolute level of Sp3 increased approximately twofold [15].
  • Krox-20 is a serum-inducible transcription activator which is possibly involved in the regulation of hindbrain development; it contains three zinc fingers similar to those of Sp1 and binds to a 9-base-pair target sequence which is related to that of Sp1 [16].

Associations of Sp1 with chemical compounds

  • Sp1 inhibition in vivo by mithramycin A leads to down-regulation of a luciferase reporter driven by the human survivin promoter in transfected cells [17].
  • The region of c-Jun mediating interaction with Sp1 was mapped within the basic region leucine zipper domain [18].
  • In both Drosophila cells and yeast, TAF110 specifically interacts with the glutamine-rich activation domains of Sp1 [6].
  • To study the molecular underpinnings of these regulatory events, we have reconstituted in vitro the synergy observed in vivo between Sp1 and the sterol-regulated factor SREBP-1a at the low density lipoprotein receptor (LDLR) promoter [19].
  • Taken together with other recent studies on the role of Sp1 in promoter activation, the current experiments suggest a unique combinatorial mechanism for promoter activation by two distinct transcription factors that are both essential to intracellular cholesterol homeostasis [20].

Physical interactions of Sp1

  • In addition, a chimeric promoter consisting of six tandem high affinity Sp1-binding sites fused with the CAT gene was transactivated by overexpressed c-Jun in HepG2 cells [18].
  • An Sp1/KLF binding site is important for the activity of a Polycomb group response element from the Drosophila engrailed gene [21].
  • We now show that Sp1 and Egr-1 bind specifically to the G+C-rich promoter sequence using in vitro deoxyribonuclease I footprinting [22].
  • A consensus nuclear factor Y (NF-Y) element was able to specifically compete for formation of the novel complex, whereas antiserum directed against the B-subunit of NF-Y supershifted the complex without disturbing binding by the Sp3/Sp1 proteins [23].
  • Regions of the Single-minded protein were fused to the DNA binding domain of the mammalian transcription factor Sp1 and shown to activate transcription from a reporter gene linked to Sp1 binding sites [24].

Regulatory relationships of Sp1

  • Developmentally controlled transcriptional regulation of myogenic cell proliferation and differentiation via expression of the fibroblast growth factor receptor 1 (FGFR1) gene is positively regulated by Sp1 and negatively regulated by E2F4-based transcriptional complexes [25].
  • The interaction of Sp1 with NF-kappaB sites thus provides a means to keep an elevated basal expression of NF-kappaB-dependent genes in the absence of activated nuclear NF-kappaB/Rel [26].
  • Using Xenopus laevis oocyte extracts to assemble chromatin in vitro, we have confirmed that Sp1 and NFkappaB can indeed induce sites hypersensitive to DNase I, micrococcal nuclease, or restriction enzymes on either side of factor binding sites in chromatin but not naked DNA [27].
  • We show that the mammalian transcription Sp1 stimulates accurate transcription in a partially fractionated RNA polymerase II-dependent system from Drosophila cultured cells [28].
  • Collectively, binding of FN to its alpha(5)beta(1) integrin activates a signal transduction pathway that results in the transcriptional activation of the alpha(5) gene likely through altering the phosphorylation state of Sp1 [29].

Other interactions of Sp1

  • We propose that this property is a reflection of the initial function of the btd/Sp1 genes that consists of establishing the fate of the ventral disc primordia and determining their pattern and growth [9].
  • These findings document the functional importance of Sp1, Sp3, and AP-2 in regulating constitutive expression of MMP-2 [30].
  • We have also analyzed the genomes of several vertebrate species, finding that the cbt orthologous genes in these organisms encode proteins that belong to the TIEG family of Sp1-like/Krüppel-like transcription factors [31].
  • Promoter selective transcriptional synergy mediated by sterol regulatory element binding protein and Sp1: a critical role for the Btd domain of Sp1 [1].
  • A cDNA clone encoding the open reading frame of NTF-1 was isolated, and the deduced primary amino acid sequence of NTF-1 includes a glutamine-rich region reminiscent of the transcriptional activation domains found in Sp1 but no recognizable DNA-binding domain [32].

Analytical, diagnostic and therapeutic context of Sp1


  1. Promoter selective transcriptional synergy mediated by sterol regulatory element binding protein and Sp1: a critical role for the Btd domain of Sp1. Athanikar, J.N., Sanchez, H.B., Osborne, T.F. Mol. Cell. Biol. (1997) [Pubmed]
  2. p53 and Sp1 interact and cooperate in the tumor necrosis factor-induced transcriptional activation of the HIV-1 long terminal repeat. Gualberto, A., Baldwin, A.S. J. Biol. Chem. (1995) [Pubmed]
  3. Interaction between transcription factors Sp1 and YY1. Seto, E., Lewis, B., Shenk, T. Nature (1993) [Pubmed]
  4. Sp1-mediated transactivation of LamC1 promoter and coordinated expression of laminin-gamma1 and Sp1 in human hepatocellular carcinomas. Liétard, J., Musso, O., Théret, N., L'Helgoualc'h, A., Campion, J.P., Yamada, Y., Clément, B. Am. J. Pathol. (1997) [Pubmed]
  5. Sp1 increases expression of cyclooxygenase-2 in hypoxic vascular endothelium. Implications for the mechanisms of aortic aneurysm and heart failure. Xu, Q., Ji, Y.S., Schmedtje, J.F. J. Biol. Chem. (2000) [Pubmed]
  6. Molecular cloning and functional analysis of Drosophila TAF110 reveal properties expected of coactivators. Hoey, T., Weinzierl, R.O., Gill, G., Chen, J.L., Dynlacht, B.D., Tjian, R. Cell (1993) [Pubmed]
  7. Mechanism of transcriptional activation by Sp1: evidence for coactivators. Pugh, B.F., Tjian, R. Cell (1990) [Pubmed]
  8. Synergistic activation by the glutamine-rich domains of human transcription factor Sp1. Courey, A.J., Holtzman, D.A., Jackson, S.P., Tjian, R. Cell (1989) [Pubmed]
  9. The role of buttonhead and Sp1 in the development of the ventral imaginal discs of Drosophila. Estella, C., Rieckhof, G., Calleja, M., Morata, G. Development (2003) [Pubmed]
  10. Common and diverged functions of the Drosophila gene pair D-Sp1 and buttonhead. Schöck, F., Purnell, B.A., Wimmer, E.A., Jäckle, H. Mech. Dev. (1999) [Pubmed]
  11. Functional interaction between p53, the TATA-binding protein (TBP), andTBP-associated factors in vivo. Farmer, G., Colgan, J., Nakatani, Y., Manley, J.L., Prives, C. Mol. Cell. Biol. (1996) [Pubmed]
  12. Detection and characterization of Sp1 binding activity in human chondrocytes and its alterations during chondrocyte dedifferentiation. Dharmavaram, R.M., Liu, G., Mowers, S.D., Jimenez, S.A. J. Biol. Chem. (1997) [Pubmed]
  13. Drosophila head segmentation factor buttonhead interacts with the same TATA box-binding protein-associated factors and in vivo DNA targets as human Sp1 but executes a different biological program. Schöck, F., Sauer, F., Jäckle, H., Purnell, B.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  14. buttonhead and D-Sp1: a novel Drosophila gene pair. Wimmer, E.A., Frommer, G., Purnell, B.A., Jäckle, H. Mech. Dev. (1996) [Pubmed]
  15. Sp1 and Sp3 activate p21 (WAF1/CIP1) gene transcription in the Caco-2 colon adenocarcinoma cell line. Gartel, A.L., Goufman, E., Najmabadi, F., Tyner, A.L. Oncogene (2000) [Pubmed]
  16. Base sequence discrimination by zinc-finger DNA-binding domains. Nardelli, J., Gibson, T.J., Vesque, C., Charnay, P. Nature (1991) [Pubmed]
  17. Molecular Mechanisms of Transactivation and Doxorubicin-mediated Repression of survivin Gene in Cancer Cells. Estève, P.O., Chin, H.G., Pradhan, S. J. Biol. Chem. (2007) [Pubmed]
  18. c-Jun transactivates the promoter of the human p21(WAF1/Cip1) gene by acting as a superactivator of the ubiquitous transcription factor Sp1. Kardassis, D., Papakosta, P., Pardali, K., Moustakas, A. J. Biol. Chem. (1999) [Pubmed]
  19. Chromatin, TAFs, and a novel multiprotein coactivator are required for synergistic activation by Sp1 and SREBP-1a in vitro. Näär, A.M., Beaurang, P.A., Robinson, K.M., Oliner, J.D., Avizonis, D., Scheek, S., Zwicker, J., Kadonaga, J.T., Tjian, R. Genes Dev. (1998) [Pubmed]
  20. Domains of transcription factor Sp1 required for synergistic activation with sterol regulatory element binding protein 1 of low density lipoprotein receptor promoter. Yieh, L., Sanchez, H.B., Osborne, T.F. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  21. An Sp1/KLF binding site is important for the activity of a Polycomb group response element from the Drosophila engrailed gene. Brown, J.L., Grau, D.J., DeVido, S.K., Kassis, J.A. Nucleic Acids Res. (2005) [Pubmed]
  22. Egr-1 and Sp1 interact functionally with the 5-lipoxygenase promoter and its naturally occurring mutants. Silverman, E.S., Du, J., De Sanctis, G.T., Rådmark, O., Samuelsson, B., Drazen, J.M., Collins, T. Am. J. Respir. Cell Mol. Biol. (1998) [Pubmed]
  23. Contrasting mammalian parathyroid hormone (PTH) promoters: nuclear factor-Y binds to a deoxyribonucleic acid element unique to the human PTH promoter and acts as a transcriptional enhancer. Alimov, A.P., Langub, M.C., Malluche, H.H., Park-Sarge, O.K., Koszewski, N.J. Endocrinology (2004) [Pubmed]
  24. Transcriptional activation domains of the single-minded bHLH protein are required for CNS midline cell development. Franks, R.G., Crews, S.T. Mech. Dev. (1994) [Pubmed]
  25. Dynamic transcriptional regulatory complexes, including E2F4, p107, p130, and Sp1, control fibroblast growth factor receptor 1 gene expression during myogenesis. Parakati, R., DiMario, J.X. J. Biol. Chem. (2005) [Pubmed]
  26. Functional interference of Sp1 and NF-kappaB through the same DNA binding site. Hirano, F., Tanaka, H., Hirano, Y., Hiramoto, M., Handa, H., Makino, I., Scheidereit, C. Mol. Cell. Biol. (1998) [Pubmed]
  27. In vitro chromatin assembly of the HIV-1 promoter. ATP-dependent polar repositioning of nucleosomes by Sp1 and NFkappaB. Widlak, P., Gaynor, R.B., Garrard, W.T. J. Biol. Chem. (1997) [Pubmed]
  28. The carboxyl-terminal repeat domain of RNA polymerase II is not required for transcription factor Sp1 to function in vitro. Zehring, W.A., Greenleaf, A.L. J. Biol. Chem. (1990) [Pubmed]
  29. Expression of the alpha 5 integrin subunit gene promoter is positively regulated by the extracellular matrix component fibronectin through the transcription factor Sp1 in corneal epithelial cells in vitro. Larouche, K., Leclerc, S., Salesse, C., Guérin, S.L. J. Biol. Chem. (2000) [Pubmed]
  30. The transcription factors Sp1, Sp3, and AP-2 are required for constitutive matrix metalloproteinase-2 gene expression in astroglioma cells. Qin, H., Sun, Y., Benveniste, E.N. J. Biol. Chem. (1999) [Pubmed]
  31. Identification and analysis of cabut orthologs in invertebrates and vertebrates. Muñoz-Descalzo, S., Belacortu, Y., Paricio, N. Dev. Genes Evol. (2007) [Pubmed]
  32. Functional analysis of NTF-1, a developmentally regulated Drosophila transcription factor that binds neuronal cis elements. Dynlacht, B.D., Attardi, L.D., Admon, A., Freeman, M., Tjian, R. Genes Dev. (1989) [Pubmed]
  33. The role of Sp1 and Sp3 in the constitutive DPYD gene expression. Zhang, X., Li, L., Fourie, J., Davie, J.R., Guarcello, V., Diasio, R.B. Biochim. Biophys. Acta (2006) [Pubmed]
  34. Selective Sp1 binding is critical for maximal activity of the human c-kit promoter. Park, G.H., Plummer, H.K., Krystal, G.W. Blood (1998) [Pubmed]
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