Abstract
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.
Keywords: 5hmC; Epigenetics; MicroRNA; TDG; Tet.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
MeSH terms
- 3' Untranslated Regions / genetics
- Animals
- Cells, Cultured
- DNA Methylation / genetics*
- DNA-Binding Proteins / antagonists & inhibitors
- DNA-Binding Proteins / genetics
- DNA-Binding Proteins / metabolism*
- Dioxygenases / antagonists & inhibitors
- Dioxygenases / genetics
- Dioxygenases / metabolism*
- Epigenetic Repression / genetics
- Gene Targeting / methods*
- HEK293 Cells
- Humans
- Mice
- MicroRNAs / antagonists & inhibitors
- MicroRNAs / physiology*
- Mixed Function Oxygenases
- Molecular Mimicry / physiology
- Oxidation-Reduction
- Protein Binding / genetics
- Proto-Oncogene Proteins / antagonists & inhibitors
- Proto-Oncogene Proteins / genetics
- Proto-Oncogene Proteins / metabolism*
- RNA, Messenger / antagonists & inhibitors
- RNA, Messenger / biosynthesis
- RNA, Messenger / genetics
- Signal Transduction / genetics*
- Thymine DNA Glycosylase / antagonists & inhibitors
- Thymine DNA Glycosylase / biosynthesis*
- Thymine DNA Glycosylase / genetics
Substances
- 3' Untranslated Regions
- DNA-Binding Proteins
- MIRN29a microRNA, human
- MicroRNAs
- Proto-Oncogene Proteins
- RNA, Messenger
- Mixed Function Oxygenases
- TET1 protein, human
- TET3 protein, human
- Dioxygenases
- TET2 protein, human
- Thymine DNA Glycosylase