TET enzymes

The TET enzymes are a family of ten-eleven translocation (TET) methylcytosine dioxygenases. They are instrumental in DNA demethylation. 5-Methylcytosine (see first Figure) is a methylated form of the DNA base cytosine (C) that often regulates gene transcription and has several other functions in the genome.[1]

DNA methylation is the addition of a methyl group to the DNA that happens at cytosine. The image shows a cytosine single ring base and a methyl group added on to the 5 carbon. In mammals, DNA methylation occurs almost exclusively at a cytosine that is followed by a guanine.

Demethylation by TET enzymes (see second Figure), can alter the regulation of transcription. The TET enzymes catalyze the hydroxylation of DNA 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), and can further catalyse oxidation of 5hmC to 5-formylcytosine (5fC) and then to 5-carboxycytosine (5caC).[2] 5fC and 5caC can be removed from the DNA base sequence by base excision repair and replaced by cytosine in the base sequence.

Demethylation of 5-methylcytosine. Demethylation of 5-methylcytosine (5mC) in neuron DNA.

TET enzymes have central roles in DNA demethylation required during embryogenesis, gametogenesis, memory, learning, addiction and pain perception.[3]

  1. ^ Wu, Xiaoji; Zhang, Yi (2017-05-30). "TET-mediated active DNA demethylation: mechanism, function and beyond". Nature Reviews Genetics. 18 (9): 517–534. doi:10.1038/nrg.2017.33. ISSN 1471-0056. PMID 28555658. S2CID 3393814.
  2. ^ Melamed P, Yosefzon Y, David C, Tsukerman A, Pnueli L (2018). "Tet Enzymes, Variants, and Differential Effects on Function". Front Cell Dev Biol. 6: 22. doi:10.3389/fcell.2018.00022. PMC 5844914. PMID 29556496.
  3. ^ Pan Z, Zhang M, Ma T, Xue ZY, Li GF, Hao LY, Zhu LJ, Li YQ, Ding HL, Cao JL (March 2016). "Hydroxymethylation of microRNA-365-3p Regulates Nociceptive Behaviors via Kcnh2". J. Neurosci. 36 (9): 2769–81. doi:10.1523/JNEUROSCI.3474-15.2016. PMC 6604871. PMID 26937014.