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Biochem Biophys Res Commun. 2013 Aug 2;437(3):368-73. doi: 10.1016/j.bbrc.2013.06.082. Epub 2013 Jun 29.

Ten-eleven translocation (Tet) and thymine DNA glycosylase (TDG), components of the demethylation pathway, are direct targets of miRNA-29a.

Author information

1
Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.

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

PMID:
23820384
PMCID:
PMC3767426
DOI:
10.1016/j.bbrc.2013.06.082
[Indexed for MEDLINE]
Free PMC Article

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