AbstractVariation in patterns of gene expression can result from modifications in the genome that occur without a change in the sequence of the DNA; such modifications include methylation of cytosine to generate 5-methylcytosine (5mC) resulting in the generation of heritable epimutation and novel epialleles. This type of non-sequence variation is called epigenetics. The enzymes responsible for generation of such DNA modifications in mammals are named DNA methyltransferases (DNMT) including DNMT1, DNMT2 and DNMT3. The later stages of oxidations to these modifications are catalyzed by Ten Eleven Translocation (TET) proteins, which contain catalytic domains belonging to the 2-oxoglutarate dependent dioxygenase family. In various mammalian cells/tissues including embryonic stem cells, cancer cells and brain tissues, it has been confirmed that these proteins are able to induce the stepwise oxidization of 5-methyl cytosine to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and finally 5-carboxylcytosine (5caC). Each stage from initial methylation until the end of the DNA demethylation process is considered as a specific epigenetic mark that may regulate gene expression. This revi
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