Abstract
The effects of the SDF1-3′A on AIDS progression have been attributed to the altered amount of stromal cell-derived factor 1 (SDF-1). However, the contribution of the SDF1-G801A polymorphism to SDF-1 expression is still unclear. In contrast to fresh peripheral blood mononuclear cells (PBMCs), Epstein–Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) express the SDF-1 mRNA. Using EBV-transformed LCLs from 42 individuals with different genotypes, we investigated the SDF-1 mRNA levels and methylation status in the SDF1 gene. Both in PBMCs and in EBV-transformed LCLs, CpG dinucleotides in the 5′ region of the SDF1 gene were unmethylated. As for the 3′ untranslated region (3′UTR), by contrast, CpG dinucleotides were methylated in PBMCs, whereas site-specific demethylation around the polymorphic site was detected in EBV-transformed LCLs. The levels of the demethylation were correlated with the SDF-1 mRNA levels. However, the genotype for the SDF1-G801A polymorphism did not significantly alter the SDF-1 mRNA levels. The allele preferences in transcription and methylation were also absent in the heterozygous cells. In conclusion, this study suggested a contribution of site-specific demethylation in the 3′UTR to the SDF1 gene expression, but did not show any evidence for the contribution of the SDF1-G801A polymorphism to the amount of the SDF-1 mRNA.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 6 digital issues and online access to articles
$119.00 per year
only $19.83 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Nagasawa T, Hirota S, Tachibana K et al. Defects of B-cell lymphopoiesis and myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 1996; 382: 635–638.
Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A, Spriger TA . A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1. J Exp Med 1996; 184: 1101–1109.
Aiuti A, Webb IJ, Bleul CC, Springer T, Gutierrez-Ramos JC . The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J Exp Med 1997; 185: 111–120.
Feng Y, Broder CC, Kennedy PE, Berger EA . HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 1996; 272: 872–877.
Bleul CC, Farzan M, Choe H et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 1996; 382: 829–833.
Oberlin E, Amara A, Bachelerie F et al. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature 1996; 382: 833–835.
Winkler C, Modi W, Smith MW et al. Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. Science 1998; 279: 389–393.
Shirozu M, Nakano T, Inazawa et al. Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene. Genomics 1995; 28: 495–500.
Hendel H, Henon N, Lebuanec H et al. Distinctive effects of CCR5, CCR2, and SDF1 genetic polymorphisms in AIDS progression. J Acq Immune Deficiency Syndromes Hum Retrovirol 1998; 19: 381–386.
Mummidi S, Ahuja SS, Gonzalez E et al. Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression. Nat Med 1998; 4: 786–793.
Marechal V, Arenzana-Seisdedos F, Heard JM, Schwartz O . Opposite effects of SDF-1 on human immunodeficiency virus type I replication. J Virol 1999; 73: 3608–3615.
Arya SK, Ginsberg CC, Davis-Warren A, D'Costa J . In vitro phenotype of SDF1 gene mutant that delays the onset of human immunodeficiency virus disease in vivo. J Hum Virol 1999; 2: 133–138.
Busslinger M, Hurst J, Flavell RA . DNA methylation and the regulation of the globin gene expression. Cell 1983; 34: 907–916.
Siegfried Z, Eden M, Feng X, Tsuberi BZ, Cedar H . DNA methylation represses transcription in vivo. Nature Genet 1999; 22: 203–206.
Arai M, Ohashi T, Tsukahara T et al. Human T-cell leukemia virus type 1 tax protein induces the expression of lymphocyte chemoattractant SDF-1/PBSF. Virology 1998; 241: 298–303.
Benboubker L, Watier H, Carion A et al. Association between the SDF1-3′A allele and high levels of CD34+ progenitor cells mobilized into peripheral blood in humans. Br J Haematol 2001; 113: 247–250.
Dubois-Laforgue D, Hendel H, Caillat-Zucman et al. A common stromal cell-derived factor-1 chemokine gene variant is associated with the early onset of type 1 diabetes. Diabetes 2001; 50: 1211–1213.
Bran-Marszak F, Fagard R, Girard B et al. Gene array identification of Epstein–Barr virus-regulated cellular genes in EBV-converted Burkitt lymphoma cell lines. Lab Invest 2002; 82: 1463–1479.
Burger JA, Tsukada N, Burger M, Zvaifler NJ, Dell'Aquila M, Kipps TJ . Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood 2000; 96: 2655–2663.
Suzuki Y, Rahman M, Mitsuya H . Diverse transcriptional response of CD4+ T cells to stromal cell-derived factor (SDF)-1: cell survival promortion and priming effects of SDF-1 on CD4+ T cells. J Immunol 2001; 167: 3064–6073.
Sei S, O'Neill DP, Stewart SK et al. Increased level of stromal cell-derived factor-1 mRNA in peripheral blood mononuclear cells from children with AIDS-related lymphoma. Cancer Res 2001; 61: 5028–5037.
Short ML, Nickel J, Schmitz A, Renkawitz R . In vivo protein interaction with the mouse M-lysozyme gene downstream enhancer correlates with demethylation and gene expression. Cell Growth Differ 1996; 7: 1545–1550.
Malumbres M, de Castro IP, Santos J, Piqueras JF, Pellicer A . Hypermethylation of the cell cycle inhibitor p15INK4b 3′-untranslated region interferes with its transcriptional regulation in primary lymphomas. Oncogene 1999; 18: 385–396.
Matsuo K, Silke J, Georgiev O, Marti P, Giovannini N, Rungger D . An embryonic demethylation mechanism involving binding of transcription factors to replicating DNA. EMBO J 1998; 17: 1446–1453.
Hsieh CL . Evidence that protein binding specifies sites of DNA demethylation. Mol Cell Biol 1999; 19: 46–56.
Lin IG, Tomzynski TJ, Ou Q, Hsieh CL . Modulation of DNA binding protein affinity directly affects target site demethylation. Mol Cell Biol 2000; 2: 2343–23499.
Ishida T, Yamamoto K . Survey of nonhuman primates for antibodies reactive with Epstein–Barr virus (EBV) antigens and susceptibility of their lymphocytes for immortalization with EBV. J Med Primatol 1987; 16: 359–371.
Kimura R, Soemantri A, Settheetham-Ishida W et al. Anthropological implication of the SDF1-3′A allele distribution in Southeast Asia and Melanesia. J Hum Genet 2002; 47: 117–121.
Clark SJ, Harrison J, Paul CL, Frommer M . High sensitivity mapping of methylated cytosines. Nucleic Acids Res 1994; 22: 2990–2997.
Author information
Authors and Affiliations
Corresponding author
Additional information
Sponsorship: Grant-in-Aid for Scientific Research on Priority Area from MEXT, Japan.
Rights and permissions
About this article
Cite this article
Kimura, R., Nishioka, T. & Ishida, T. The SDF1-G801A polymorphism is not associated with SDF1 gene expression in Epstein–Barr virus-transformed lymphoblastoid cells. Genes Immun 4, 356–361 (2003). https://doi.org/10.1038/sj.gene.6363978
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gene.6363978
Keywords
This article is cited by
-
Significance of CXCL12 in Type 2 Diabetes Mellitus and Its Associated Complications
Inflammation (2015)
-
CXCL12, CXCR4 and IFNγ genes expression: implications for proinflammatory microenvironment of breast cancer
Clinical and Experimental Medicine (2013)
-
Increased Circulating Levels of SDF-1 (CXCL12) in Type 2 Diabetic Patients Are Correlated to Disease State but Are Unrelated to Polymorphism of the SDF-1β Gene in the Iranian Population
Inflammation (2012)
-
Association of the SDF1-3′A polymorphism with susceptibility to myocardial infarction in Chinese Han population
Molecular Biology Reports (2010)
-
SDF1-3'A Gene Polymorphism is Associated with Laryngeal Cancer
Pathology & Oncology Research (2010)