TET3

TET3 (ten-eleven translocation 3) is an Fe(II)/α-ketoglutarate-dependent dioxygenase that catalyzes the iterative oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), thereby contributing to active DNA demethylation and epigenetic regulation^[1]. TET3 participates in biological processes linked to zygote formation, embryogenesis, neural function, and genome-wide methylation turnover through pathways coupled to thymine-DNA glycosylase-mediated base excision repair^[1]. Mechanistically, TET3-mediated oxidation products, particularly 5fC and 5caC, can be removed and restored to unmethylated cytosine, enabling dynamic control of gene expression programs^[1]. In developmental and disease-relevant contexts, dysregulation of TET family activity has been associated with multiple pathological states, highlighting the importance of TET3-dependent epigenetic homeostasis^[1]. Compared with the related isoform TET2, TET3 contains an N-terminal CXXC DNA-binding domain, which directly contributes to chromatin targeting and substrate recognition^[1][2]. Furthermore, full-length TET3 exhibits preferential binding of its CXXC domain to 5caC-containing CpG sequences, indicating a distinctive capacity to recognize products of its own catalytic pathway and potentially influence locus-specific demethylation events^[2]. TET3 exists as multiple isoforms, including full-length and shorter variants, providing additional regulatory diversity in different cellular contexts^[2]. For experimental applications, modulation of TET activity and analysis of TET3-dependent DNA hydroxymethylation are widely used to investigate epigenetic remodeling, developmental biology, and neurobiology-related mechanisms^[1][2].

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