Autor: |
J, Yang, C, Deng, N, Hemati, S M, Hanash, B C, Richardson |
Rok vydání: |
1997 |
Předmět: |
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Zdroj: |
Journal of immunology (Baltimore, Md. : 1950). 159(3) |
ISSN: |
0022-1767 |
Popis: |
DNA methylation, a mechanism modifying gene expression, is mediated in part by the enzyme DNA methyltransferase. Reduced levels of T cell DNA methyltransferase have been observed in lupus-like diseases, and increased levels have been reported in malignancies. Little is known concerning the regulation of human DNA methyltransferase. In this report we demonstrate that mitogenic T cell stimulation causes an increase in DNA methyltransferase mRNA and enzyme activity. We also show that pharmacologic inhibition of T cell DNA methylation causes an increase in the rate of DNA methyltransferase mRNA transcription and a corresponding increase in mRNA levels and enzyme activity. This suggests that DNA methyltransferase is itself regulated in part by DNA methylation status, possibly representing a feedback mechanism. DNA methylation inhibition also resulted in an increase in Ha-ras and c-jun mRNA levels, overexpression of which increases DNA methyltransferase in murine systems. These results thus identify two mechanisms regulating levels of human T cell DNA methyltransferase and raise the possibility that abnormalities in either could contribute to disorders associated with altered DNA methylation. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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