Ten-eleven translocation (Tet) and thymine DNA glycosylase (TDG), components of the demethylation pathway, are direct targets of miRNA-29a
Copyright policy )Ten-eleven translocation (Tet) and thymine DNA glycosylase (TDG), components of the demethylation pathway, are direct targets of miRNA-29a
The ten-eleven translocation family of proteins (Tet1/2/3, Tets) converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which can be further oxidized and repaired by thymine DNA glycosylase (TDG), to influence gene transcription in embryonic and adult tissues. However the mechanisms of how Tets and TDG levels are regulated are unknown. We show that miR-29 can directly regulate Tet1-3 and TDG mRNA levels through binding to their 3'UTRs. miR-29 mimic decreases global 5hmC levels, a hallmark of Tet activity. Moreover, the mRNA levels for Tet3 and TDG are inversely correlated with the levels of miR-29 in aged mouse aorta implying that aging may affect methylation patterns via miRNA. In summary, our data show that Tets and TDG are direct targets of miR-29 and unravel a novel regulatory role for this miRNA in epigenetic DNA demethylation pathways.
- Yale University United States
Molecular Mimicry, DNA Methylation, Epigenetic Repression, Thymine DNA Glycosylase, Dioxygenases, Mixed Function Oxygenases, DNA-Binding Proteins, Mice, MicroRNAs, HEK293 Cells, Proto-Oncogene Proteins, Gene Targeting, Animals, Humans, RNA, Messenger, 3' Untranslated Regions, Oxidation-Reduction, Cells, Cultured, Protein Binding, Signal Transduction
Molecular Mimicry, DNA Methylation, Epigenetic Repression, Thymine DNA Glycosylase, Dioxygenases, Mixed Function Oxygenases, DNA-Binding Proteins, Mice, MicroRNAs, HEK293 Cells, Proto-Oncogene Proteins, Gene Targeting, Animals, Humans, RNA, Messenger, 3' Untranslated Regions, Oxidation-Reduction, Cells, Cultured, Protein Binding, Signal Transduction
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