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Originally published In Press as doi:10.1074/jbc.C100343200 on September 10, 2001

J. Biol. Chem., Vol. 276, Issue 43, 39508-39511, October 26, 2001
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ACCELERATED PUBLICATION
Interleukin-6 Regulation of the Human DNA Methyltransferase (HDNMT) Gene in Human Erythroleukemia Cells*

David R. HodgeDagger §, Weihua XiaoDagger §, Peter A. Clausen||, Gisela Heidecker**, Moshe SzyfDagger Dagger , and William L. Farrar§

From the Dagger  Intramural Research Support Program, SAIC Frederick and the Cytokine Molecular Mechanisms Section, § Laboratory of Molecular Immunoregulation, NCI-Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, Maryland 21702, the || Invitrogen Corporation, Gaithersburg, Maryland 20852, the ** Laboratory of Leukocyte Biology, NCI-Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, Maryland 21702, and the Dagger Dagger  Department of Pharmacology, McGill University, Montreal, Quebec H3G 1Y6, Canada

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; Ramchandani, 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.

* This work was supported in whole or in part with Federal funds from the NCI, National Institutes of Health, under Contract NO1-CO-56000 and sponsored in part by the NCI, Department of Health and Human Services, under a contract with SAIC. The content of this publication does not necessarily reflect the views or policies of the Department of Health and human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: NCI, NIH, P. O. Box B, Bldg. 560, Rm. 31-76, Frederick, MD 21702. Tel.: 301-846-6865; Fax: 301-846-7042; E-mail: hodge@mail.ncifcrf.gov.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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