ausblenden:
Schlagwörter:
3' Untranslated Regions/genetics
Animals
Cells, Cultured
DNA Methylation/*genetics
DNA-Binding Proteins/antagonists & inhibitors/genetics/*metabolism
Dioxygenases/antagonists & inhibitors/genetics/*metabolism
Epigenetic Repression/genetics
Gene Targeting/*methods
HEK293 Cells
Humans
Mice
MicroRNAs/antagonists & inhibitors/*physiology
Molecular Mimicry/physiology
Oxidation-Reduction
Protein Binding/genetics
Proto-Oncogene Proteins/antagonists & inhibitors/genetics/*metabolism
RNA, Messenger/antagonists & inhibitors/biosynthesis/genetics
Signal Transduction/*genetics
Thymine DNA Glycosylase/antagonists & inhibitors/*biosynthesis/genetics
5hmC
Epigenetics
MicroRNA
Tdg
Tet
Zusammenfassung:
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.