File:TET-mediated DNA modifications and demethylation.png
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[edit]DescriptionTET-mediated DNA modifications and demethylation.png |
FIGURE 1. TET-mediated DNA modifications and demethylation. (A) Unmodified cytosine (C) is methylated by DNA methyltransferases (DNMTs) at the 5 position to become 5-methylcytosine (5mC). TET proteins oxidize 5mC into 5-hydroxymethylcytosine (5hmC), a stable epigenetic mark, and subsequently to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). TET can demethylate DNA via replication-dependent (passive) or replication-independent (active) mechanisms. (B) Left, passive DNA demethylation. DNMT1/UHRF1 complex recognizes 5mC at the hemi-methylated CpG motif during DNA replication and methylates the unmodified cytosine on the newly synthesized DNA strand (left; pink strand). However, the oxidized ethylcytosines 5hmC, 5fC, and 5caC (together, oxi-mC) are not recognized by DNMT1/UHRF1, resulting in unmodified cytosine on the new DNA strand. Further DNA replication in the presence of continuing TET activity will result in progressive dilution of 5mC in the daughter cells. Right panel, active DNA demethylation. While 5hmC is stable and persists in the genome, 5fC and 5caC can be recognized and excised by thymine DNA glycosylase (TDG), and the resulting abasic sites are repaired as unmodified C by base excision repair (BER). Other mechanisms (e.g., decarboxylation of 5caC) have been suggested but have not yet been proven to exist. (C) The approximate abundance of unmodified and modified cytosines in the haploid human/mouse genome. About 5% of cytosine is methylated (5mC); in most cells, the vast majority of 5mC is present at CG dinucleotides although it is low at CpG islands. 5hmC amounts to about 1-10% of 5mC (estimated at 10% here as in embryonic stem cells), while the levels of 5fC and 5caC are each about an order of magnitude lower than the previous oxidative modification. It is not known whether the low levels of 5fC and 5caC are due to features of TET enzymes that cause them to arrest at 5hmC, or to their continuing removal by TDG or other mechanisms. |
Date | |
Source | Enzymes and 5hmC in Adaptive and Innate Immune Systems. Front. Immunol. 10:210 doi: 10.3389/fimmu.2019.00210 |
Author | Lio C-WJ and Rao A |
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Copyright © 2019 Lio and Rao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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current | 21:17, 23 May 2024 | 1,587 × 1,115 (358 KB) | Rasbak (talk | contribs) | {{Information |description= FIGURE 1. TET-mediated DNA modifications and demethylation. (A) Unmodified cytosine (C) is methylated by DNA methyltransferases (DNMTs) at the 5 position to become 5-methylcytosine (5mC). TET proteins oxidize 5mC into 5-hydroxymethylcytosine (5hmC), a stable epigenetic mark, and subsequently to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). TET can demethylate DNA via replication-dependent (passive) or replication-independent (active) mechanisms. (B) Left, pas... |
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