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Demethylation of Non-CpG Sites in DNA Is Initiated by TET2 5-Methylcytosine Dioxygenase
| Content Provider | MDPI |
|---|---|
| Author | Dey, Aninda Sundar Bhattacharya, Chayan Guan, Yihong Jha, Babal Kant Mukherji, Mridul |
| Copyright Year | 2021 |
| Description | In the mammalian genome, cytosine methylation predominantly occurs at CpG sites. In addition, a number of recent studies have uncovered extensive C5 cytosine methylation (5mC) at non-CpG (5mCpH, where H = A/C/T) sites. Little is known about the enzyme responsible for active demethylation of 5mCpH sites. Using a very sensitive and quantitative LC–MS/MS method, we demonstrate that the human TET2, an iron (II)- and 2OG-dependent dioxygenase, which is a frequently mutated gene in several myeloid malignancies, as well as in a number of other types of cancers, can oxidize 5mCpH sites in double-stranded DNA in vitro. Similar to oxidation of 5mCpG, oxidation of 5mC at CpH sites produces 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxycytosine (5caC) bases in DNA. After 5mCpG, which is the most preferred substrate, TET2 prefers 5mCpC as a substrate, followed by 5mCpA and then 5mCpT. Since the TDG/BER pathway and deformylation or decarboxylation of 5fC or 5caC, respectively, can convert 5fCpH and 5caCpH to an unmodified cytosine base in DNA, our results suggest a novel demethylation pathway of 5mCpH sites initiated by TET2 dioxygenase. |
| Ending Page | 36 |
| Page Count | 11 |
| Starting Page | 26 |
| e-ISSN | 26738856 |
| DOI | 10.3390/dna1010004 |
| Journal | DNA |
| Issue Number | 1 |
| Volume Number | 1 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-09-21 |
| Access Restriction | Open |
| Subject Keyword | DNA Dna Cell Biology Epigenetics Dna Demethylation Tet Dioxygenases Substrate Specificity 5-methylcytosine Oxidation Non-cpg Demethylation |
| Content Type | Text |
| Resource Type | Article |
