Skip to main content
SpringerLink
Log in

New putative control elements in the promoter of the gene for the CXCL13 chemokine, a target of the alternative NF-κB pathway

  • Cell Molecular Biology
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

The proximal promoter region of the gene for the CXCL13/BLC chemokine has been studied by electrophoretic mobility shift assay and reporter gene analysis in order to detect new control elements, in particular, NF-κB binding sites. Two new putative control elements have been identified. One of them contains a Rel/NF-κB binding site and seems to participate in inducible gene expression. The other is an Sp1 factor binding site, essential for basal transcription. It is the first time that such a site is found in the promoter of a target gene of the alternative NF-κB pathway. This finding indicates that genes under the control of the alternative NF-κB pathway can be cooperatively regulated by Rel/NF-κB and Sp1. Our results will add to the understanding of the signaling pathways that govern the expression of genes controlled by the alternative NF-κB pathway.

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. Hayden M.S., Ghosh S. 2008. Shared principles in NF-κB signaling. Cell. 132, 344–362.

    Article  PubMed  CAS  Google Scholar 

  2. Bonizzi G., Karin M. 2004. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 25, 280–288.

    Article  PubMed  CAS  Google Scholar 

  3. Hayden M.S., West A.P., Ghosh S. 2006. NF-kappaB and the immune response. Oncogene. 25, 6758–6780.

    Article  PubMed  CAS  Google Scholar 

  4. Gerondakis S., Grumont R., Gugasyan R., Wong L., Isomura I., Ho W., Banerjee A. 2006. Unravelling the complexities of the NF-kappaB signalling pathway using mouse knockout and transgenic models. Oncogene. 25, 6781–6799.

    Article  PubMed  CAS  Google Scholar 

  5. Pasparakis M., Luedde T., Schmidt-Supprian M. 2006. Dissection of the NF-kappaB signalling cascade in transgenic and knockout mice. Cell Death Differ. 13, 861–872.

    Article  PubMed  CAS  Google Scholar 

  6. Dejardin E., Droin N.M., Delhase M., Haas E., Cao Y., Makris C., Li Z.W., Karin M., Ware C.F., Green D.R. 2002. The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Immunity. 17, 525–535.

    Article  PubMed  CAS  Google Scholar 

  7. Ware C.F. 2005. Network communications: Lymphotoxins, LIGHT, and TNF. Annu. Rev. Immunol. 23, 787–819.

    Article  PubMed  CAS  Google Scholar 

  8. Dejardin E. 2006. The alternative NF-kappaB pathway from biochemistry to biology: Pitfalls and promises for future drug development. Biochem. Pharmacol. 72, 1161–1179.

    Article  PubMed  CAS  Google Scholar 

  9. Natoli G., De Santa F. 2006. Shaping alternative NF-κB-dependent gene expression programs: New clues to specificity. Cell Death Differ. 13, 693–696.

    Article  PubMed  CAS  Google Scholar 

  10. Ansel K.M., Ngo V.N., Hyman P.L., Luther S.A., Forster R., Sedgwick J.D., Browning J.L., Lipp M., Cyster J.G. 2000. A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature. 406, 309–314.

    Article  PubMed  CAS  Google Scholar 

  11. Finke D., Acha-Orbea H., Mattis A., Lipp M., Kraehenbuhl J. 2002. CD4+ CD3- cells induce Peyer’s patch development: role of alpha4beta1 integrin activation by CXCR5. Immunity. 17, 363–373.

    Article  PubMed  CAS  Google Scholar 

  12. Forster R., Mattis A.E., Kremmer E., Wolf E., Brem G., Lipp M. 1996. A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. Cell. 87, 1037–1047.

    Article  PubMed  CAS  Google Scholar 

  13. Luther S.A., Ansel K.M., Cyster J.G. 2003. Overlapping roles of CXCL13, interleukin 7 receptor alpha, and CCR7 ligands in lymph node development. J. Exp. Med. 197, 1191–1198.

    Article  PubMed  CAS  Google Scholar 

  14. Coope H.J., Atkinson P.G., Huhse B., Belich M., Janzen J., Holman M.J., Klaus G.G., Johnston L.H., Ley S.C. 2002. CD40 regulates the processing of NFkappaB2 p100 to p52. EMBO J. 21, 5375–5385.

    Article  PubMed  CAS  Google Scholar 

  15. Siebenlist U., Brown K., Claudio E. 2005. Control of lymphocyte development by nuclear factor-kappaB. Nature Rev. Immunol. 5, 435–445.

    Article  CAS  Google Scholar 

  16. Weih F., Caamano J. 2003. Regulation of secondary lymphoid organ development by the nuclear factor-kappaB signal transduction pathway. Immunol. Rev. 195, 91–105.

    Article  PubMed  CAS  Google Scholar 

  17. Bonizzi G., Bebien M., Otero D.C., Johnson-Vroom K.E., Cao Y., Vu D., Jegga A.G., Aronow B.J., Ghosh G., Rickert R.C., Karin M. 2004. Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers. EMBO J. 23, 4202–4210.

    Article  PubMed  CAS  Google Scholar 

  18. Britanova L.V., Makeev V.J., Kuprash D.V. 2008. In vitro selection of optimal RelB/p52 DNA-binding motifs. Biochem. Biophys. Res. Commun. 365, 583–588.

    Article  PubMed  CAS  Google Scholar 

  19. Dynan W.S., Tjian R. 1983. The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell. 35, 79–87.

    Article  PubMed  CAS  Google Scholar 

  20. Marin M., Karis A., Visser P., Grosveld F., Philipsen S. 1997. Transcription factor Sp1 is essential for early embryonic development but dispensable for cell growth and differentiation. Cell. 89, 619–628.

    Article  PubMed  CAS  Google Scholar 

  21. Bouwman P., Philipsen S. 2002. Regulation of the activity of Sp1-related transcription factors. Mol. Cell. Endocrinol. 195, 27–38.

    Article  PubMed  CAS  Google Scholar 

  22. Suske G., Bruford E., Philipsen S. 2005. Mammalian SP/KLF transcription factors: bring in the family. Genomics. 85, 551–556.

    Article  PubMed  CAS  Google Scholar 

  23. Zhao C., Meng A. 2005. Sp1-like transcription factors are regulators of embryonic development in vertebrates. Dev. Growth Differ. 47, 201–211.

    Article  PubMed  CAS  Google Scholar 

  24. Yao P.L., Lin Y.C., Sawhney P., Richburg J.H. 2007. Transcriptional regulation of FasL expression and participation of sTNF-alpha in response to Sertoli cell injury. J. Biol. Chem. 282, 5420–5431.

    Article  PubMed  CAS  Google Scholar 

  25. Zhu N.L., Li C., Huang H.H., Sebald M., Londhe V.A., Heisterkamp N., Warburton D., Bellusci S., Minoo P. 2007. TNF-alpha represses transcription of human Bone Morphogenetic Protein-4 in lung epithelial cells. Gene. 393, 70–80.

    Article  PubMed  CAS  Google Scholar 

  26. Yan Y., Dalmasso G., Sitaraman S., Merlin D. 2007. Characterization of the human intestinal CD98 promoter and its regulation by interferon-gamma. Am. J. Physiol. Gastrointest. Liver Physiol. 292, G535–G545.

    Article  PubMed  CAS  Google Scholar 

  27. Baetu T.M., Kwon H., Sharma S., Grandvaux N., Hiscott J. 2001. Disruption of NF-kappaB signaling reveals a novel role for NF-kappaB in the regulation of TNF-related apoptosis-inducing ligand expression. J. Immunol. 167, 3164–3173.

    PubMed  CAS  Google Scholar 

  28. Xu J., Zhou J.Y., Wu G.S. 2006. Tumor necrosis factor-related apoptosis-inducing ligand is required for tumor necrosis factor alpha-mediated sensitization of human breast cancer cells to chemotherapy. Cancer Res. 66, 10092–10099.

    Article  PubMed  CAS  Google Scholar 

  29. Tone Y., Kojima Y., Furuuchi K., Brady M., Yashiro-Ohtani Y., Tykocinski M.L., Tone M. 2007. OX40 gene expression is up-regulated by chromatin remodeling in its promoter region containing Sp1/Sp3, YY1, and NFkappa B binding sites. J. Immunol. 179, 1760–1767.

    PubMed  CAS  Google Scholar 

  30. Xu Y., Fang F., Dhar S.K., St Clair W.H., Kasarskis E.J., St Clair D.K. 2007. The role of a single-stranded nucleotide loop in transcriptional regulation of the human sod2 gene. J. Biol. Chem. 282, 15981–15994.

    Article  PubMed  CAS  Google Scholar 

  31. Shi Q., Le X., Abbruzzese J.L., Peng Z., Qian C.N., Tang H., Xiong Q., Wang B., Li X.C., Xie K. 2001. Constitutive Sp1 activity is essential for differential constitutive expression of vascular endothelial growth factor in human pancreatic adenocarcinoma. Cancer Res. 61, 4143–4154.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Engelgardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia

    L. V. Britanova & D. V. Kuprash

Authors
  1. L. V. Britanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. V. Kuprash
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. V. Kuprash.

Additional information

Original Russian Text © L.V. Britanova, D.V. Kuprash, 2009, published in Molekulyarnaya Biologiya, 2009, Vol. 43, No. 4, pp. 657–665.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Britanova, L.V., Kuprash, D.V. New putative control elements in the promoter of the gene for the CXCL13 chemokine, a target of the alternative NF-κB pathway. Mol Biol 43, 604–611 (2009). https://doi.org/10.1134/S0026893309040128

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893309040128

Key words

Search

Navigation