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Interleukin-6 regulation of the human DNA methyltransferase (HDNMT) gene in human erythroleukemia cells

  1. Author:
    Hodge, D. R.
    Xiao, W. H.
    Clausen, P. A.
    Heidecker, G.
    Szyf, M.
    Farrar, W. L.

  2. Author Address

    NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, NIH, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, NIH, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Cytokine Mol Mechanisms Sect, NIH, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, NIH, Frederick, MD 21702 USA. Invitrogen Corp, Gaithersburg, MD 20852 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Leukocyte Biol, NIH, Frederick, MD 21702 USA. McGill Univ, Dept Pharmacol, Montreal, PQ H3G 1Y6, Canada. Hodge DR NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, NIH, Frederick, MD 21702 USA.
    1. Year: 2001
  2. Journal: Journal of Biological Chemistry
    1. 276
    2. 43
    3. Pages: 39508-39511
  4. Type of Article: Article
  1. Abstract:

    Methylation of mammalian DNA by the DNA methyltransferase enzyme (dnmt-1) at CpG dinucleotide sequences has been recognized as an important epigenetic control mechanism in regulating the expression of cellular genes (Yen, R. W., Vertino, P. M., Nelkin, B. D., Yu, J. J., el-Deiry, W., Cumaraswamy, A., Lennon, G. G., Trask, B. J., Celano, P., and Baylin, S. B. (1992) Nucleic Acids Res. 20, 2287-2291; Ramehandani, S., Bigey, P., and Szyf, M. (1998) Biol. Chem. 379, 535-5401). Here we show that interleukin (IL)-6 regulates the methyltransferase promoter and resulting enzyme activity, which requires transcriptional activation by the Fli-1 transcription factor (Spyropoulos, D. D., Pharr, P. N., Lavenburg, K. R., Jackers, P., Papas, T. S., Ogawa, M., and Watson, D. K. (1998) Mol. Cell. Biol. 15, 5643-5652). The data suggest that inflammatory cytokines such as IL-6 may exert many epigenetic changes in cells via the regulation of the methyltransferase gene. Furthermore, IL-6 regulation of transcription factors like Fli-1, which can help to direct cells along opposing differentiation pathways, may in fact be reflected in part by their ability to regulate the methylation of cellular genes.

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