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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

GC Rich Sequence

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Disease relevance of GC Rich Sequence

  • OBJECTIVE: To identify one nuclear autoantigenic protein within a complex of DNA binding proteins that bind to GC-rich sequences in Epstein-Barr virus and cellular DNA, and to describe the clinical characteristics of patients whose sera contained autoantibodies to this novel autoantigen [1].
  • Previous studies have shown that the adenovirus 12S E1A oncoprotein represses the TGF-beta 1 promoter by targeting an adjacent (-90 to -81) but different GC-rich sequence (TGGGTGGGG) [2].
  • Vent exo- resolves highly GC-rich sequence substantially better than Thermus aquaticus DNA polymerase (Taq) and with a similar efficiency as Pfu exo-. The DNA/DNA polymerase activity ratio is significantly higher for Vent exo- than for Pfu exo-, which is reflected by the sensibility of Vent exo- in efficiently amplifying genomic DNA [3].

High impact information on GC Rich Sequence

  • We have cloned a human cDNA that encodes a factor that binds to the GC-rich sequences present in the epidermal growth factor receptor (EGFR), beta-actin, and calcium-dependent protease (CANP) promoters [4].
  • Functional analysis of the 2.2 kb TF 5' promoter indicated that a GC-rich region containing three copies each of the EGR-1 and Sp1 sites was required for induction [5].
  • Three cis-acting elements in the KAR2 promoter control expression of KAR2: (i) a GC-rich region that contributes to the high level of constitutive expression, (ii) a functional heat shock element (HSE) and (iii) an element (UPR) that is involved in the induction of BiP mRNA by unfolded proteins [6].
  • However, in the most homologous region, a GC-rich sequence is inserted in the A. nidulans intron, flanked by two direct repeats of 5 bp [7].
  • Other GC-rich sequences coding for some polyalanine domains were found to be polymorphic in human [8].

Biological context of GC Rich Sequence


Anatomical context of GC Rich Sequence


Associations of GC Rich Sequence with chemical compounds


Gene context of GC Rich Sequence

  • Lying between these two elements is a GC-rich region that is similar in sequence to the consensus element for binding of the mammalian transcription factor Sp1 and that is involved in the basal expression of the KAR2 gene [24].
  • Three types of sites function independently of the nitrogen source: two clusters of Abflp- and Rap1p-binding sites, and a GC-rich sequence [25].
  • Several lines of evidence show that CUGBP1 induces the translation of p21 via binding to a GC-rich sequence located within the 5' region of p21 mRNA [26].
  • The results from transcription assays demonstrated that Vpr augments promoter activity of p21 through the GC-rich region located between nucleotides -84 and -74 with respect to the +1 transcription start site [27].
  • Moreover, direct DNA binding of BMP-responsive Smads and common-partner Smad4 to the GC-rich sequence of PBE was observed [28].

Analytical, diagnostic and therapeutic context of GC Rich Sequence


  1. The transcriptional activator Sp1, a novel autoantigen. Spain, T.A., Sun, R., Gradzka, M., Lin, S.F., Craft, J., Miller, G. Arthritis Rheum. (1997) [Pubmed]
  2. HPV16 E6 oncoprotein stimulates the transforming growth factor-beta 1 promoter in fibroblasts through a specific GC-rich sequence. Dey, A., Atcha, I.A., Bagchi, S. Virology (1997) [Pubmed]
  3. Optimal conditions and specific characteristics of Vent exo- DNA polymerase in ligation-mediated polymerase chain reaction protocols. Vigneault, F., Drouin, R. Biochem. Cell Biol. (2005) [Pubmed]
  4. Molecular cloning and characterization of a human DNA binding factor that represses transcription. Kageyama, R., Pastan, I. Cell (1989) [Pubmed]
  5. Shear stress induction of the tissue factor gene. Lin, M.C., Almus-Jacobs, F., Chen, H.H., Parry, G.C., Mackman, N., Shyy, J.Y., Chien, S. J. Clin. Invest. (1997) [Pubmed]
  6. A 22 bp cis-acting element is necessary and sufficient for the induction of the yeast KAR2 (BiP) gene by unfolded proteins. Mori, K., Sant, A., Kohno, K., Normington, K., Gething, M.J., Sambrook, J.F. EMBO J. (1992) [Pubmed]
  7. The mitochondrial genome of the fission yeast Schizosaccharomyces pombe: highly homologous introns are inserted at the same position of the otherwise less conserved cox1 genes in Schizosaccharomyces pombe and Aspergillus nidulans. Lang, B.F. EMBO J. (1984) [Pubmed]
  8. Polymorphism, shared functions and convergent evolution of genes with sequences coding for polyalanine domains. Lavoie, H., Debeane, F., Trinh, Q.D., Turcotte, J.F., Corbeil-Girard, L.P., Dicaire, M.J., Saint-Denis, A., Pagé, M., Rouleau, G.A., Brais, B. Hum. Mol. Genet. (2003) [Pubmed]
  9. Distinct DNase-I hypersensitive sites are associated with TAL-1 transcription in erythroid and T-cell lines. Leroy-Viard, K., Vinit, M.A., Lecointe, N., Mathieu-Mahul, D., Roméo, P.H. Blood (1994) [Pubmed]
  10. Activating transcription factor 3 and early growth response 1 are the novel targets of LY294002 in a phosphatidylinositol 3-kinase-independent pathway. Yamaguchi, K., Lee, S.H., Kim, J.S., Wimalasena, J., Kitajima, S., Baek, S.J. Cancer Res. (2006) [Pubmed]
  11. The promoter of the long variant of collagen XVIII, the precursor of endostatin, contains liver-specific regulatory elements. Liétard, J., Théret, N., Rehn, M., Musso, O., Dargère, D., Pihlajaniemi, T., Clément, B. Hepatology (2000) [Pubmed]
  12. Differentiation-induced gene expression in 3T3-L1 preadipocytes. Characterization of a differentially expressed gene encoding stearoyl-CoA desaturase. Ntambi, J.M., Buhrow, S.A., Kaestner, K.H., Christy, R.J., Sibley, E., Kelly, T.J., Lane, M.D. J. Biol. Chem. (1988) [Pubmed]
  13. The human gC1qR/p32 gene, C1qBP. Genomic organization and promoter analysis. Tye, A.J., Ghebrehiwet, B., Guo, N., Sastry, K.N., Chow, B.K., Peerschke, E.I., Lim, B.L. J. Biol. Chem. (2001) [Pubmed]
  14. Involvement of the Sp3 transcription factor in induction of p21Cip1/WAF1 in keratinocyte differentiation. Prowse, D.M., Bolgan, L., Molnár, A., Dotto, G.P. J. Biol. Chem. (1997) [Pubmed]
  15. In vivo footprinting of the enhancer sequences in the upstream long terminal repeat of Moloney murine leukemia virus: differential binding of nuclear factors in different cell types. Granger, S.W., Fan, H. J. Virol. (1998) [Pubmed]
  16. Expression of the testis-specific histone H1t gene: evidence for involvement of multiple cis-acting promoter elements. Wolfe, S.A., van Wert, J.M., Grimes, S.R. Biochemistry (1995) [Pubmed]
  17. Regulation of human IL-18 gene expression: interaction of PU.1 with GC-box binding protein is involved in human IL-18 expression in myeloid cells. Koyama, N., Hoelzer, D., Ottmann, O.G. Eur. J. Immunol. (2004) [Pubmed]
  18. Cyclic adenosine monophosphate (cAMP) stimulation of the kit ligand promoter in sertoli cells requires an Sp1-binding region, a canonical TATA box, and a cAMP-induced factor binding to an immediately downstream GC-rich element. Grimaldi, P., Capolunghi, F., Geremia, R., Rossi, P. Biol. Reprod. (2003) [Pubmed]
  19. Evolution and regulation of the gene encoding superoxide dismutase from the archaebacterium Halobacterium cutirubrum. May, B.P., Dennis, P.P. J. Biol. Chem. (1989) [Pubmed]
  20. Nuclear factor ETF specifically stimulates transcription from promoters without a TATA box. Kageyama, R., Merlino, G.T., Pastan, I. J. Biol. Chem. (1989) [Pubmed]
  21. Rho-dependent termination of transcription. II. Kinetics of mRNA elongation during transcription from the bacteriophage lambda PR promoter. Morgan, W.D., Bear, D.G., von Hippel, P.H. J. Biol. Chem. (1983) [Pubmed]
  22. Up-regulation of Na,K-ATPase beta 1 transcription by hyperoxia is mediated by SP1/SP3 binding. Wendt, C.H., Gick, G., Sharma, R., Zhuang, Y., Deng, W., Ingbar, D.H. J. Biol. Chem. (2000) [Pubmed]
  23. Structural relationships of low molecular weight viral RNAs synthesized by RNA polymerase III in nuclei from adenovirus 2-infected cells. Harris, B., Roeder, R.G. J. Biol. Chem. (1978) [Pubmed]
  24. The promoter region of the yeast KAR2 (BiP) gene contains a regulatory domain that responds to the presence of unfolded proteins in the endoplasmic reticulum. Kohno, K., Normington, K., Sambrook, J., Gething, M.J., Mori, K. Mol. Cell. Biol. (1993) [Pubmed]
  25. Combinatorial regulation of the Saccharomyces cerevisiae CAR1 (arginase) promoter in response to multiple environmental signals. Smart, W.C., Coffman, J.A., Cooper, T.G. Mol. Cell. Biol. (1996) [Pubmed]
  26. Molecular basis for impaired muscle differentiation in myotonic dystrophy. Timchenko, N.A., Iakova, P., Cai, Z.J., Smith, J.R., Timchenko, L.T. Mol. Cell. Biol. (2001) [Pubmed]
  27. Interplay between HIV-1 Vpr and Sp1 modulates p21(WAF1) gene expression in human astrocytes. Amini, S., Saunders, M., Kelley, K., Khalili, K., Sawaya, B.E. J. Biol. Chem. (2004) [Pubmed]
  28. Smad6 is a Smad1/5-induced smad inhibitor. Characterization of bone morphogenetic protein-responsive element in the mouse Smad6 promoter. Ishida, W., Hamamoto, T., Kusanagi, K., Yagi, K., Kawabata, M., Takehara, K., Sampath, T.K., Kato, M., Miyazono, K. J. Biol. Chem. (2000) [Pubmed]
  29. In vivo footprinting of the human 11beta-hydroxysteroid dehydrogenase type 2 promoter: evidence for cell-specific regulation by Sp1 and Sp3. Nawrocki, A.R., Goldring, C.E., Kostadinova, R.M., Frey, F.J., Frey, B.M. J. Biol. Chem. (2002) [Pubmed]
  30. Sp1 mediates glucose activation of the acetyl-CoA carboxylase promoter. Daniel, S., Kim, K.H. J. Biol. Chem. (1996) [Pubmed]
  31. The human T-cell leukemia virus-1 transcriptional activator Tax enhances cAMP-responsive element-binding protein (CREB) binding activity through interactions with the DNA minor groove. Lundblad, J.R., Kwok, R.P., Laurance, M.E., Huang, M.S., Richards, J.P., Brennan, R.G., Goodman, R.H. J. Biol. Chem. (1998) [Pubmed]
  32. Estrogen regulation of vascular endothelial growth factor gene expression in ZR-75 breast cancer cells through interaction of estrogen receptor alpha and SP proteins. Stoner, M., Wormke, M., Saville, B., Samudio, I., Qin, C., Abdelrahim, M., Safe, S. Oncogene (2004) [Pubmed]
  33. In vitro cytotoxicity of GC sequence directed alkylating agents related to distamycin. Lee, M., Rhodes, A.L., Wyatt, M.D., D'Incalci, M., Forrow, S., Hartley, J.A. J. Med. Chem. (1993) [Pubmed]
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