TET3 (E6J8A) Rabbit mAb #99980

Methylation of DNA at cytosine residues is a heritable, epigenetic modification that is critical for proper regulation of gene expression, genomic imprinting, and mammalian development (1,2). 5-methylcytosine is a repressive epigenetic mark established de novo by two enzymes, DNMT3a and DNMT3b, and is maintained by DNMT1 (3,4). 5-methylcytosine was originally thought to be passively depleted during DNA replication. However, subsequent studies have shown that Ten-Eleven Translocation (TET) proteins TET1, TET2, and TET3 can catalyze the oxidation of methylated cytosine to 5-hydroxymethylcytosine (5-hmC) (5). Additionally, TET proteins can further oxidize 5-hmC to form 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC), both of which are excised by thymine-DNA glycosylase (TDG), effectively linking cytosine oxidation to the base excision repair pathway and supporting active cytosine demethylation (6,7). TET3 plays several key roles in regulating early development and neonatal growth. First, TET3 functions to demethylate DNA in the male pronucleus of the zygote following fertilization (8-10). In addition, TET3 binds to and regulates numerous developmental genes later during development (11). TET2/TET3 deficiency can lead to myeloid cell, B cell, and invariant natural killer T (iNKT) cell malignancies. In Tregs, TET2/TET3 deficiency in mice leads to hyperproliferation and inflammatory disease, with decreased expression of Treg-specific genes and increased expression of genes involved in proliferation and cancer (12,13).