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The importance of eukaryotic DNA methylation [5-methylcytosine (5mC)] in transcriptional regulation and development was first suggested almost 40 years ago. However, the molecular mechanism underlying the dynamic nature of this epigenetic mark was not understood until recently, following the discovery that the TET proteins, a family of AlkB-like Fe(II)/α-ketoglutarate-dependent dioxygenases, can oxidize 5mC to generate 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Since then, several mechanisms that are responsible for processing oxidized 5mC derivatives to achieve DNA demethylation have emerged. Our biochemical understanding of the DNA demethylation process has prompted new investigations into the biological functions of DNA demethylation. Characterization of two additional AlkB family proteins, FTO and ALKBH5, showed that they possess demethylase activity toward N(6)-methyladenosine (m(6)A) in RNA, indicating that members of this subfamily of dioxygenases have a general function in demethylating nucleic acids. In this review, we discuss recent advances in this emerging field, focusing on the mechanism and function of TET-mediated DNA demethylation.

Original publication

DOI

10.1146/annurev-biochem-060713-035513

Type

Book

Publication Date

2014

Volume

83

Pages

585 - 614

Keywords

5-methylcytosine oxidation, DNA/RNA demethylation, Fe(II)/α-ketoglutarate-dependent dioxygenases, N6-methyladenosine, Tet, 5-Methylcytosine, Animals, Cytosine, DNA, DNA Methylation, Escherichia coli, Gene Expression Regulation, Genome, Germ Cells, HEK293 Cells, Humans, Methylation, Mice, Neoplasms, Oxygen, RNA, Stem Cells, Transcriptome