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. 1997 Jan 15;25(2):339–346. doi: 10.1093/nar/25.2.339

Distamycin prolongs E-selectin expression by interacting with a specific NF-kappaB-HMG-I(Y) binding site in the promoter.

P Ghersa 1, J Whelan 1, Y Cambet 1, J F DeLamarter 1, R Hooft van Huijsduijnen 1
PMCID: PMC146425  PMID: 9016563

Abstract

The E-selectin cell adhesion protein plays a critical role in mediating adherence of leukocytes to endothelium at sites of inflammation. Cytokine-induced E-selectin expression on the surface of endothelial cells is transient; mRNA expression peaks at 3-4 h after induction and returns to basal levels within 24 h. The mechanism for this transcriptional down-modulation is not known. Promoter binding factors responsible for induced gene expression include NF-kappaB, which binds at three sites within the E-selectin promoter, and HMG-I(Y), which binds to the A/T-rich core found at the centre of these binding sites. Distamycin is an antibiotic that also binds A/T-rich DNA and inhibits HMG-I(Y) DNA binding. To study the role of HMG-I(Y) in E-selectin expression, we have examined the effect of distamycin on the cytokine-induced E-selectin expression cycle. We found that distamycin prolonged E-selectin expression, both by sustaining mRNA transcription and by extending the transcript's half-life. The distamycin effect on transcription was mediated through one of the three NF-kappaB-HMG-I(Y) binding sites (NF-kappaBII) within the promoter. This suggests that the NF-kappaB-HMG-I(Y) complex interacting at the NF-kappaBII site plays a role not only in cytokine induction of E-selectin expression, but also in its down-modulation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Becker-André M., Hooft van Huijsduijnen R., Losberger C., Whelan J., Delamarter J. F. Murine endothelial leukocyte-adhesion molecule 1 is a close structural and functional homologue of the human protein. Eur J Biochem. 1992 Jun 1;206(2):401–411. doi: 10.1111/j.1432-1033.1992.tb16940.x. [DOI] [PubMed] [Google Scholar]
  2. Bevilacqua M. P. Endothelial-leukocyte adhesion molecules. Annu Rev Immunol. 1993;11:767–804. doi: 10.1146/annurev.iy.11.040193.004003. [DOI] [PubMed] [Google Scholar]
  3. Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
  4. Broggini M., Erba E., Ponti M., Ballinari D., Geroni C., Spreafico F., D'Incalci M. Selective DNA interaction of the novel distamycin derivative FCE 24517. Cancer Res. 1991 Jan 1;51(1):199–204. [PubMed] [Google Scholar]
  5. Brown A. M., Linhoff M. W., Stein B., Wright K. L., Baldwin A. S., Jr, Basta P. V., Ting J. P. Function of NF-kappa B/Rel binding sites in the major histocompatibility complex class II invariant chain promoter is dependent on cell-specific binding of different NF-kappa B/Rel subunits. Mol Cell Biol. 1994 May;14(5):2926–2935. doi: 10.1128/mcb.14.5.2926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chiang S. Y., Welch J., Rauscher F. J., 3rd, Beerman T. A. Effects of minor groove binding drugs on the interaction of TATA box binding protein and TFIIA with DNA. Biochemistry. 1994 Jun 14;33(23):7033–7040. doi: 10.1021/bi00189a003. [DOI] [PubMed] [Google Scholar]
  7. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  8. Collins T. Analysis of the ELAM-1 and VCAM-1 promoters--tools to target gene expression in endothelium in transgenic animals. J Vasc Surg. 1992 May;15(5):923–924. doi: 10.1016/0741-5214(92)90752-t. [DOI] [PubMed] [Google Scholar]
  9. Collins T., Read M. A., Neish A. S., Whitley M. Z., Thanos D., Maniatis T. Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers. FASEB J. 1995 Jul;9(10):899–909. [PubMed] [Google Scholar]
  10. Collins T., Williams A., Johnston G. I., Kim J., Eddy R., Shows T., Gimbrone M. A., Jr, Bevilacqua M. P. Structure and chromosomal location of the gene for endothelial-leukocyte adhesion molecule 1. J Biol Chem. 1991 Feb 5;266(4):2466–2473. [PubMed] [Google Scholar]
  11. Du W., Maniatis T. An ATF/CREB binding site is required for virus induction of the human interferon beta gene [corrected]. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2150–2154. doi: 10.1073/pnas.89.6.2150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Du W., Maniatis T. The high mobility group protein HMG I(Y) can stimulate or inhibit DNA binding of distinct transcription factor ATF-2 isoforms. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11318–11322. doi: 10.1073/pnas.91.24.11318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Feriotto G., Mischiati C., Bianchi N., Passadore M., Gambari R. Binding of distamycin and chromomycin to human immunodeficiency type 1 virus DNA: a non-radioactive automated footprinting study. Eur J Pharmacol. 1995 Jul 18;290(2):85–93. doi: 10.1016/0922-4106(95)90020-9. [DOI] [PubMed] [Google Scholar]
  14. Fisher R. P., Lisowsky T., Parisi M. A., Clayton D. A. DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein. J Biol Chem. 1992 Feb 15;267(5):3358–3367. [PubMed] [Google Scholar]
  15. Gerritsen M. E., Bloor C. M. Endothelial cell gene expression in response to injury. FASEB J. 1993 Apr 1;7(6):523–532. doi: 10.1096/fasebj.7.6.8472891. [DOI] [PubMed] [Google Scholar]
  16. Ghersa P., Hooft van Huijsduijnen R., Whelan J., DeLamarter J. F. Labile proteins play a dual role in the control of endothelial leukocyte adhesion molecule-1 (ELAM-1) gene regulation. J Biol Chem. 1992 Sep 25;267(27):19226–19232. [PubMed] [Google Scholar]
  17. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Grilli M., Chiu J. J., Lenardo M. J. NF-kappa B and Rel: participants in a multiform transcriptional regulatory system. Int Rev Cytol. 1993;143:1–62. doi: 10.1016/s0074-7696(08)61873-2. [DOI] [PubMed] [Google Scholar]
  19. Grosschedl R., Giese K., Pagel J. HMG domain proteins: architectural elements in the assembly of nucleoprotein structures. Trends Genet. 1994 Mar;10(3):94–100. doi: 10.1016/0168-9525(94)90232-1. [DOI] [PubMed] [Google Scholar]
  20. Hession C., Osborn L., Goff D., Chi-Rosso G., Vassallo C., Pasek M., Pittack C., Tizard R., Goelz S., McCarthy K. Endothelial leukocyte adhesion molecule 1: direct expression cloning and functional interactions. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1673–1677. doi: 10.1073/pnas.87.5.1673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hooft van Huijsduijnen R. A. PCR-generated probes for the study of DNA-protein interactions. Biotechniques. 1992 Jun;12(6):830–832. [PubMed] [Google Scholar]
  22. Hooft van Huijsduijnen R., Li X. Y., Black D., Matthes H., Benoist C., Mathis D. Co-evolution from yeast to mouse: cDNA cloning of the two NF-Y (CP-1/CBF) subunits. EMBO J. 1990 Oct;9(10):3119–3127. doi: 10.1002/j.1460-2075.1990.tb07509.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hooft van Huijsduijnen R., Pescini R., DeLamarter J. F. Two distinct NF-kappa B complexes differing in their larger subunit bind the E-selectin promoter kappa B element. Nucleic Acids Res. 1993 Aug 11;21(16):3711–3717. doi: 10.1093/nar/21.16.3711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hooft van Huijsduijnen R., Whelan J., Pescini R., Becker-André M., Schenk A. M., DeLamarter J. F. A T-cell enhancer cooperates with NF-kappa B to yield cytokine induction of E-selectin gene transcription in endothelial cells. J Biol Chem. 1992 Nov 5;267(31):22385–22391. [PubMed] [Google Scholar]
  25. Iademarco M. F., McQuillan J. J., Dean D. C. Vascular cell adhesion molecule 1: contrasting transcriptional control mechanisms in muscle and endothelium. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3943–3947. doi: 10.1073/pnas.90.9.3943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Iademarco M. F., McQuillan J. J., Rosen G. D., Dean D. C. Characterization of the promoter for vascular cell adhesion molecule-1 (VCAM-1). J Biol Chem. 1992 Aug 15;267(23):16323–16329. [PubMed] [Google Scholar]
  27. Ip Y. T. Transcriptional regulation. Converting an activator into a repressor. Curr Biol. 1995 Jan 1;5(1):1–3. doi: 10.1016/s0960-9822(95)00001-7. [DOI] [PubMed] [Google Scholar]
  28. Kaszubska W., Hooft van Huijsduijnen R., Ghersa P., DeRaemy-Schenk A. M., Chen B. P., Hai T., DeLamarter J. F., Whelan J. Cyclic AMP-independent ATF family members interact with NF-kappa B and function in the activation of the E-selectin promoter in response to cytokines. Mol Cell Biol. 1993 Nov;13(11):7180–7190. doi: 10.1128/mcb.13.11.7180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kim J., Klooster S., Shapiro D. J. Intrinsically bent DNA in a eukaryotic transcription factor recognition sequence potentiates transcription activation. J Biol Chem. 1995 Jan 20;270(3):1282–1288. doi: 10.1074/jbc.270.3.1282. [DOI] [PubMed] [Google Scholar]
  30. Kim J., Zwieb C., Wu C., Adhya S. Bending of DNA by gene-regulatory proteins: construction and use of a DNA bending vector. Gene. 1989 Dec 21;85(1):15–23. doi: 10.1016/0378-1119(89)90459-9. [DOI] [PubMed] [Google Scholar]
  31. Korb J., Stokrová J., Ríman J., Sulová A. Avian myeloblastosis virus core-bound 7 S DNA, highly bent minute structures with sequence-directed curvature. Acta Virol. 1993 Oct;37(5):343–359. [PubMed] [Google Scholar]
  32. Lavigne M., Herbert M., Kolb A., Buc H. Upstream curved sequences influence the initiation of transcription at the Escherichia coli galactose operon. J Mol Biol. 1992 Mar 20;224(2):293–306. doi: 10.1016/0022-2836(92)90995-v. [DOI] [PubMed] [Google Scholar]
  33. Lehming N., Thanos D., Brickman J. M., Ma J., Maniatis T., Ptashne M. An HMG-like protein that can switch a transcriptional activator to a repressor. Nature. 1994 Sep 8;371(6493):175–179. doi: 10.1038/371175a0. [DOI] [PubMed] [Google Scholar]
  34. Lewis H., Kaszubska W., DeLamarter J. F., Whelan J. Cooperativity between two NF-kappa B complexes, mediated by high-mobility-group protein I(Y), is essential for cytokine-induced expression of the E-selectin promoter. Mol Cell Biol. 1994 Sep;14(9):5701–5709. doi: 10.1128/mcb.14.9.5701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Liptay S., Schmid R. M., Nabel E. G., Nabel G. J. Transcriptional regulation of NF-kappa B2: evidence for kappa B-mediated positive and negative autoregulation. Mol Cell Biol. 1994 Dec;14(12):7695–7703. doi: 10.1128/mcb.14.12.7695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Meacock S., Pescini-Gobert R., DeLamarter J. F., Hooft van Huijsduijnen R. Transcription factor-induced, phased bending of the E-selectin promoter. J Biol Chem. 1994 Dec 16;269(50):31756–31762. [PubMed] [Google Scholar]
  37. Neish A. S., Williams A. J., Palmer H. J., Whitley M. Z., Collins T. Functional analysis of the human vascular cell adhesion molecule 1 promoter. J Exp Med. 1992 Dec 1;176(6):1583–1593. doi: 10.1084/jem.176.6.1583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Oliveira I. C., Mukaida N., Matsushima K., Vilcek J. Transcriptional inhibition of the interleukin-8 gene by interferon is mediated by the NF-kappa B site. Mol Cell Biol. 1994 Aug;14(8):5300–5308. doi: 10.1128/mcb.14.8.5300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Pober J. S., Cotran R. S. Cytokines and endothelial cell biology. Physiol Rev. 1990 Apr;70(2):427–451. doi: 10.1152/physrev.1990.70.2.427. [DOI] [PubMed] [Google Scholar]
  40. Radic M. Z., Saghbini M., Elton T. S., Reeves R., Hamkalo B. A. Hoechst 33258, distamycin A, and high mobility group protein I (HMG-I) compete for binding to mouse satellite DNA. Chromosoma. 1992 Oct;101(10):602–608. doi: 10.1007/BF00360537. [DOI] [PubMed] [Google Scholar]
  41. Reeves R. Chromatin changes during the cell cycle. Curr Opin Cell Biol. 1992 Jun;4(3):413–423. doi: 10.1016/0955-0674(92)90006-x. [DOI] [PubMed] [Google Scholar]
  42. Reeves R., Nissen M. S. The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure. J Biol Chem. 1990 May 25;265(15):8573–8582. [PubMed] [Google Scholar]
  43. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993 Apr 29;362(6423):801–809. doi: 10.1038/362801a0. [DOI] [PubMed] [Google Scholar]
  44. Schindler U., Baichwal V. R. Three NF-kappa B binding sites in the human E-selectin gene required for maximal tumor necrosis factor alpha-induced expression. Mol Cell Biol. 1994 Sep;14(9):5820–5831. doi: 10.1128/mcb.14.9.5820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Smith G. M., Whelan J., Pescini R., Ghersa P., DeLamarter J. F., Hooft van Huijsduijnen R. DNA-methylation of the E-selectin promoter represses NF-kappa B transactivation. Biochem Biophys Res Commun. 1993 Jul 15;194(1):215–221. doi: 10.1006/bbrc.1993.1806. [DOI] [PubMed] [Google Scholar]
  46. Supakar P. C., Jung M. H., Song C. S., Chatterjee B., Roy A. K. Nuclear factor kappa B functions as a negative regulator for the rat androgen receptor gene and NF-kappa B activity increases during the age-dependent desensitization of the liver. J Biol Chem. 1995 Jan 13;270(2):837–842. doi: 10.1074/jbc.270.2.837. [DOI] [PubMed] [Google Scholar]
  47. Swerlick R. A., Lee K. H., Li L. J., Sepp N. T., Caughman S. W., Lawley T. J. Regulation of vascular cell adhesion molecule 1 on human dermal microvascular endothelial cells. J Immunol. 1992 Jul 15;149(2):698–705. [PubMed] [Google Scholar]
  48. Thanos D., Maniatis T. NF-kappa B: a lesson in family values. Cell. 1995 Feb 24;80(4):529–532. doi: 10.1016/0092-8674(95)90506-5. [DOI] [PubMed] [Google Scholar]
  49. Whelan J., Ghersa P., Hooft van Huijsduijnen R., Gray J., Chandra G., Talabot F., DeLamarter J. F. An NF kappa B-like factor is essential but not sufficient for cytokine induction of endothelial leukocyte adhesion molecule 1 (ELAM-1) gene transcription. Nucleic Acids Res. 1991 May 25;19(10):2645–2653. doi: 10.1093/nar/19.10.2645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Whitley M. Z., Thanos D., Read M. A., Maniatis T., Collins T. A striking similarity in the organization of the E-selectin and beta interferon gene promoters. Mol Cell Biol. 1994 Oct;14(10):6464–6475. doi: 10.1128/mcb.14.10.6464. [DOI] [PMC free article] [PubMed] [Google Scholar]

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