Figure 1. Regulation of TETs/methylcytosine oxidation.

TET proteins can be regulated at multiple levels, all having a potential impact on global or local methylcytosine oxidation. Small molecules such as 2-hydroxyglutarate (2-HG) or hydrogen peroxide (H₂O₂) inhibit the catalytic activity of TETs while others, such as vitamin C, enhance their activity. Similarly, small microRNAs (miRs) can also affect TET-mediated 5hmC formation by direct downregulation of TET expression. Finally, TETs are connected to and regulated by chromatin related proteins. For example, TET bind the OGT GlcNAc transferase, which can glycosylate and possibly stabilize TETs.