FIG. 2.

Factors involved in regulation of TET2 gene expression and enzyme activity. Transcription factors (NFYB, C/EBPα, Oct4) regulate TET2 mRNA levels in various developmental stages or cell types. microRNA inhibited TET protein expression in post-transcription level. TET protein can also be regulated by O-linked N-acetylglucosamine transferase or cullin-RING ubiquitin ligase 4-CRL4VprBP, acetyltransferase p300 in post-transcription level. IDAX results in TET2 protein degradation through caspase activation. Vitamin C acts as a cofactor for Fe2⁺ and 2-OG-dependent TET dioxygenase and can directly enhance the catalytic activity of TET protein. Pathological accumulation of three metabolites, namely, 2-hydroxyglutarete (2-HG), succinate, and fumarate, which are structurally similar to α-OG, leading to a competitive inhibition of α-OG-dependent TET activity. NFYB, nuclear transcriptional factor Y subunit beta.