Tet2
Developmental stage
Expressed at high levels in early embryos from 1-cell stage until at least blastula (PubMed:24357321). Expressed during embryonic development in both somatic and primordial germ cells from 9.5 dpc, with a peak in primordial germ cells at 16.5 dpc (PubMed:23151479).
Function
Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for 5-hydroxymethylcytosine in CpG motifs. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT.
Post-translational modifications
May be glycosylated. It is unclear whether interaction with OGT leads to GlcNAcylation. According to a report, it is GlcNAcylated by OGT (PubMed:23352454). In contrast, another group reports no GlcNAcylation by OGT in human ortholog.
Monoubiquitinated at Lys-1212 by the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CRL4(VprBP) or CUL4A-RBX1-DDB1-DCAF1/VPRBP complex; this modification promotes binding to DNA.
Sequence Similarities
Belongs to the TET family.
Tissue Specificity
Expressed in the brain, kidney, heart, lung, muscle and stomach (PubMed:16722336, PubMed:24357321). Expressed in germinal vesicle (GV) stage and MII-stage oocytes and in early embryos (PubMed:24357321). Present in embryonic stem cells (ES cells) (PubMed:20639862).
Cellular localization
- Nucleus
- Chromosome
- Localization to chromatin depends upon monoubiquitination at Lys-1212.
Alternative names
Kiaa1546, Tet2, Methylcytosine dioxygenase TET2, Protein Ayu17-449