title: miR-29 represses the activities of DNA methyltransferases and DNA demethylases.
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.
authors.affiliation: Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan. msumiyo@gunma-u.ac.jp
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Morita
authors.forename: Takuro
authors.initials: T
authors.lastname: Horii
authors.forename: Mika
authors.initials: M
authors.lastname: Kimura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya
authors.forename: Shoji
authors.initials: S
authors.lastname: Tajima
authors.forename: Izuho
authors.initials: I
authors.lastname: Hatada
mesh_terms: D020413:3' Untranslated Regions; D045744:Cell Line, Tumor; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D006899:Mixed Function Oxygenases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D044502:Thymine DNA Glycosylase / Q000235:genetics / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
chemical_list: D020413:3' Untranslated Regions; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D006899:Mixed Function Oxygenases; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D044502:Thymine DNA Glycosylase; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C532045:MIRN29a microRNA, human; C462539:TET1 protein, human