Skip to main content
SpringerLink
Log in

Normal Transcription of the C1 Inhibitor Gene is Dependent Upon a Polypurine⋅Polypyrimidine Region Within the Promoter

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Analysis of the transcriptional activity of C1 inhibitor (C1INH) promoter reporter constructs with mutations in the R⋅Y region indicate that triplex formation by this region is not a predictor of transcriptional activity and that normal promoter function depends on the interaction of trans acting factors with specific elements within this region. Electrophoretic mobility shift assay (EMSA) of Hep3B nuclear extracts using the wild type promoter probe (nucleotides −98 to −9) yielded four major bands. Incubation of the same extracts with probes lacking the HNF-1 site resulted in the disappearance of one band. Supershift assays indicate that HNF-1α is the only previously identified protein that is present in the EMSA bands. Southwestern blot analysis detected four bands (Mr's ∼130, 75, 65 and 20 kDa). These data suggest that the −98 to −9 region of the C1INH promoter interacts with at least four proteins, one of which is HNF-1α.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Forbes, C. D., J. Pensky, and O. D. Ratnoff. 1970. Inhibition of activated Hageman factor and activated plasma thromboplastin antecedent by purified serum C1 inactivator. J. Lab. Clin. Med. 76:809.

    Google Scholar 

  2. Ratnoff, O. D., J. Pensky, D. Ogston, and G. B. Naff. 1969. The inhibition of plasmin, plasma kallikrein, plasma permeability factor, and the C′1r subcomponent of the first component of complement by serum C′1 esterase inhibitor. J. Exp. Med. 129:315.

    Google Scholar 

  3. Bock, S. C., K. Skriver, E. Nielsen, H. C. Thogersen, B. Wiman, V. H. Donaldson, R. L. Eddy, J. Marrinan, E. Radziejewska, R. Huber, and et al. 1986. Human C1 inhibitor: primary structure, cDNA cloning, and chromosomal localization. Biochemistry. 25:4292.

    Google Scholar 

  4. Zahedi, K., A. E. Prada, and A. E. Davis, 3rd. 1994. Transcriptional regulation of the C1 inhibitor gene by gamma-interferon. J.Biol. Chem. 269:9669.

    Google Scholar 

  5. Zahedi, K., J. J. Bissler, A. E. Prada, J. A. Prada, and A. E. Davis, 3rd. 1999. The promoter of the C1 inhibitor gene contains a polypurine.polypyrimidine segment that enhances transcriptional activity. J. of Immunol. 162:7249.

    Google Scholar 

  6. Galibert, M. D., Y. Miyagoe, and T. Meo. 1993. E-box activator of the C4 promoter is related to but distinct from the transcription factor upstream stimulating factor. J. Immunol. 151:6099.

    Google Scholar 

  7. Galibert, M. D., L. Boucontet, C. R. Goding, and T. Meo. 1997.Recognition of the E-C4 element from the C4 complement gene promoter by the upstream stimulatory factor-1 transcription factor.J. Immunol. 159:6176.

    Google Scholar 

  8. Miyagoe, Y., M. D. Galibert, E. Georgatsou, G. Fourel, and T. Meo. 1994. Promoter elements of the mouse complement C4 gene critical for transcription activation and start site location. J. Biol.Chem. 269:8268.

    Google Scholar 

  9. Zenzie-Gregory, B., P. Sheridan, K. A. Jones, and S. T. Smale. 1993. HIV-1 core promoter lacks a simple initiator element but contains a bipartite activator at the transcription start site. J. Biol.Chem. 268:15823.

    Google Scholar 

  10. Carcamo, J., L. Buckbinder, and D. Reinberg. 1991. The initiator directs the assembly of a transcription factor IID-dependent transcription complex. Proc. Natl. Acad. Sci. USA 88:8052.

    Google Scholar 

  11. Cheriyath, V., C. D. Novina, and A. L. Roy. 1998. TFII-I regulates Vbeta promoter activity through an initiator element. Mol. Cell.Biol. 18:4444.

    Google Scholar 

  12. Davis, T. L., A. B. Firulli, and A. J. Kinniburgh. 1989. Ribonucleoprotein and protein factors bind to an H-DNA-forming c-myc DNA element: possible regulators of the c-myc gene. Proc. Natl.Acad. Sci. USA. 86:9682.

    Google Scholar 

  13. Schroth, G. P. and P. S. Ho. 1995. Occurrence of potential cruciform and H-DNA forming sequences in genomic DNA. Nucleic Acids Res. 23:1977.

    Google Scholar 

  14. Karlovsky, P., P. Pecinka, M. Vojtiskova, E. Makaturova, and E. Palecek. 1990. Protonated triplex DNA in E. coli cells as detected by chemical probing. FEBS Lett. 274:39.

    Google Scholar 

  15. Kohwi, Y., S. R. Malkhosyan, and T. Kohwi-Shigematsu. 1992.Intramolecular dG.dG.dC triplex detected in Escherichia coli cells. J. Mol. Biol. 223:817.

    Google Scholar 

  16. Ussery, D. W. and R. R. Sinden. 1993. Environmental influences on the in vivo level of intramolecular triplex DNA in Escherichia coli. Biochemistry. 32:6206.

    Google Scholar 

  17. Boles, T. C. and M. E. Hogan. 1987. DNA structure equilibria in the human c-myc gene. Biochemistry. 26:367.

    Google Scholar 

  18. Christophe, D., B. Cabrer, A. Bacolla, H. Targovnik, V. Pohl, and G. Vassart. 1985. An unusually long poly(purine).poly(pyrimidine) sequence is located upstream from the human thyroglobulin gene.Nucleic Acids Res. 13:5127.

    Google Scholar 

  19. Hoffman, E. K., S. P. Trusko, M. Murphy, and D. L. George. 1990.An S1 nuclease-sensitive homopurine /homopyrimidine domain in the c-Ki-ras promoter interacts with a nuclear factor. Proc. Natl.Acad. Sci. USA. 87:2705.

    Google Scholar 

  20. Gilmour, D. S., G. H. Thomas, and S. C. Elgin. 1989. Drosophila nuclear proteins bind to regions of alternating C and T residues in gene promoters. Science. 245:1487.

    Google Scholar 

  21. Glaser, R. L., G. H. Thomas, E. Siegfried, S. C. Elgin, and J.T. Lis. 1990. Optimal heat-induced expression of the Drosophila hsp26 gene requires a promoter sequence containing (CT)n.(GA)n repeats. J. Mol. Biol. 211:751.

    Google Scholar 

  22. Kinniburgh, A. J. 1989. A cis-acting transcription element of the c-myc gene can assume an H-DNA conformation [published erratum appears in Nucleic Acids Res 1989 Oct 25;17(20):8412].Nucleic Acids Res. 17:7771.

    Google Scholar 

  23. Sakatsume, O., H. Tsutsui, Y. Wang, H. Gao, X. Tang, T. Yamauchi, T. Murata, K. Itakura, and K. K. Yokoyama. 1996.Binding of THZif-1, a MAZ-like zinc finger protein to the nuclease-hypersensitive element in the promoter region of the c-MYC protooncogene. J. Biol. Chem. 271:31322.

    Google Scholar 

  24. Takimoto, M., T. Tomonaga, M. Matunis, M. Avigan, H. Krutzsch, G. Dreyfuss, and D. Levens. 1993. Specific binding of heterogeneous ribonucleoprotein particle protein K to the human c-myc promoter, in vitro. J. Biol. Chem. 268:18249.

    Google Scholar 

  25. Postel, E. H., S. J. Berberich, S. J. Flint, and C. A. Ferrone. 1993. Human c-myc transcription factor PuF identified as nm23-H2 nucleoside diphosphate kinase, a candidate suppressor of tumor metastasis [see comments]. Science. 261:478.

    Google Scholar 

  26. Kochetkova, M. and M. F. Shannon. 1996. DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells. J. Biol. Chem. 271:14438.

    Google Scholar 

  27. DesJardins, E. and N. Hay. 1993. Repeated CT elements bound by zinc finger proteins control the absolute and relative activities of the two principal human c-myc promoters.Mol. Cell. Biol. 13:5710.

    Google Scholar 

  28. Chen, A., A. Reyes, and R. Akeson. 1993. A homopurine:homopyrimidine sequence derived from the rat neuronal cell adhesion molecule-encoding gene alters expression in transient transfections.Gene. 128:211.

    Google Scholar 

  29. Chen, S., P. C. Supakar, R. L. Vellanoweth, C. S. Song, B. Chatterjee, and A. K. Roy. 1997. Functional role of a conformationally flexible homopurine /homopyrimidine domain of the androgen receptor gene promoter interacting with Sp1 and a pyrimidine single strand DNA-binding protein. Mol. Endocrinol. 11:3.

    Google Scholar 

  30. Zahedi, K., A. E. Prada, J. A. Prada, and A. E. Davis, 3rd. 1997.Characterization of the IFN-gamma-responsive element in the 5′ flanking region of the C1 inhibitor gene.J. Immunol. 159:6091.

    Google Scholar 

  31. Michelotti, E. F., S. Sanford, J. M. P. Freije, N. J. MacDonald, P. S. Steeg, and D. Levens. 1997. Nm23 /PuF does not directly stimulate transcription through the CT element in vivo. J. Biol.Chem. 272:22526.

    Google Scholar 

  32. Bossone, S. A., C. Asselin, A. J. Patel, and K. B. Marcu. 1992. MAZ, a zinc finger protein, binds to c-MYC and C2 gene sequences regulating transcriptional initiation and termination.Proc. Natl. Acad. Sci. USA. 89:7452.

    Google Scholar 

  33. Chae, S. K., N. S. Lee, K. J. Lee, and E. Kim. 1998. Transactivation potential of the C-terminus of human Nm23-H1. FEBS Lett. 423:235.

    Google Scholar 

  34. Ji, L., M. Arcinas, and L. M. Boxer. 1995. The transcription factor, Nm23H2, binds to and activates the translocated c-myc allele in Burkitt's lymphoma. J. Biol. Chem. 270:13392.

    Google Scholar 

  35. Postel, E. H., V. H. Weiss, J. Beneken, and A. Kirtane. 1996.Mutational analysis of NM23-H2 /NDP kinase identifies the structural domains critical to recognition of a c-myc regulatory element. Proc. Natl. Acad. Sci. USA. 93:6892.

    Google Scholar 

  36. Frain, M.,G. Swart, P. Monaci, A. Nicosia, S. Stampfli, R. Frank, and R. Cortese. 1989. The liver-specific transcription factor LFB1 contains a highly diverged homeobox DNA binding domain.Cell. 59:145.

    Google Scholar 

  37. Mendel, D. B. and G. R. Crabtree. 1991. HNF-1, a member of a novel class of dimerizing homeodomain proteins. J. Biol. Chem. 266:677.

    Google Scholar 

  38. Xanthopoulos, K. G., V. R. Prezioso, W. S. Chen, F. M. Sladek, R. Cortese, and J. E. Darnell, Jr. 1991. The different tissue transcription patterns of genes for HNF-1, C /EBP, HNF-3, and HNF-4, protein factors that govern liver-specific transcription. Proc. Natl.Acad. Sci. USA. 88:3807.

    Google Scholar 

  39. Soutoglou, E., G. Papafotiou, N. Katrakili, and I. Talianidis. 2000.Transcriptional activation by hepatocyte nuclear factor-1 requires synergism between multiple coactivator proteins. J. Biol. Chem. 275:12515.

    Google Scholar 

  40. Matunis, M. J., W. M. Michael, and G. Dreyfuss. 1992. Characterization and primary structure of the poly(C)-binding heterogeneous nuclear ribonucleoprotein complex K protein. Mol. Cell. Biol. 12:164.

    Google Scholar 

  41. Du, Q., I. N. Melnikova, and P. D. Gardner. 1998. Differential effects of heterogeneous nuclear ribonucleoprotein K on Sp1-and Sp3-mediated transcriptional activation of a neuronal nicotinic acetylcholine receptor promoter. J. Biol. Chem. 273:19877.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology and Hypertension, Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, Ohio, 45229

    Kamyar Zahedi, Anne E. Prada & Jorge A. Prada

  2. Center for Blood Research, 800 Huntington Avenue, Boston, Massachusetts, 02115

    Aideen Mulligan & Alvin E. Davis III

Authors
  1. Kamyar Zahedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne E. Prada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aideen Mulligan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jorge A. Prada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alvin E. Davis III
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zahedi, K., Prada, A.E., Mulligan, A. et al. Normal Transcription of the C1 Inhibitor Gene is Dependent Upon a Polypurine⋅Polypyrimidine Region Within the Promoter. Inflammation 26, 183–191 (2002). https://doi.org/10.1023/A:1016519813252

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1016519813252

Search

Navigation