Effect of mitogenic stimulation and DNA methylation on human T cell DNA methyltransferase expression and activity
| Autor: | J Yang, C Deng, N Hemati, S M Hanash, B C Richardson |
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| Rok vydání: | 1997 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 159:1303-1309 |
| ISSN: | 1550-6606 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 |
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