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miR-29 Represses the Activities of DNA Methyltransferases and DNA Demethylases
Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Laboratory of Epigenetics, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan
* Author to whom correspondence should be addressed.
Received: 29 May 2013; in revised form: 25 June 2013 / Accepted: 25 June 2013 / Published: 12 July 2013
Abstract: Members of the microRNA-29 (miR-29) family directly target the DNA methyltransferases, DNMT3A and DNMT3B. Disturbances in the expression levels of miR-29 have been linked to tumorigenesis and tumor aggressiveness. Members of the miR-29 family are currently thought to repress DNA methylation and suppress tumorigenesis by protecting against de novo methylation. Here, we report that members of the miR-29 family repress the activities of DNA methyltransferases and DNA demethylases, which have opposing roles in control of DNA methylation status. Members of the miR-29 family directly inhibited DNA methyltransferases and two major factors involved in DNA demethylation, namely tet methylcytosine dioxygenase 1 (TET1) and thymine DNA glycosylase (TDG). Overexpression of miR-29 upregulated the global DNA methylation level in some cancer cells and downregulated DNA methylation in other cancer cells, suggesting that miR-29 suppresses tumorigenesis by protecting against changes in the existing DNA methylation status rather than by preventing de novo methylation of DNA.
Keywords: cancer; DNA demethylation; microRNA; miR-29; TDG; TET1
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Morita, S.; Horii, T.; Kimura, M.; Ochiya, T.; Tajima, S.; Hatada, I. miR-29 Represses the Activities of DNA Methyltransferases and DNA Demethylases. Int. J. Mol. Sci. 2013, 14, 14647-14658.
Morita S, Horii T, Kimura M, Ochiya T, Tajima S, Hatada I. miR-29 Represses the Activities of DNA Methyltransferases and DNA Demethylases. International Journal of Molecular Sciences. 2013; 14(7):14647-14658.
Morita, Sumiyo; Horii, Takuro; Kimura, Mika; Ochiya, Takahiro; Tajima, Shoji; Hatada, Izuho. 2013. "miR-29 Represses the Activities of DNA Methyltransferases and DNA Demethylases." Int. J. Mol. Sci. 14, no. 7: 14647-14658.