Emerging roles of TET proteins and 5-hydroxymethylcytosines in active DNA demethylation and beyond

Tight correlation of 5-hydroxymethylcytosine and Polycomb marks in health and disease

“…41,42 The role of 5hmC in epigenetic regulation appears to be regulated by a complex network of enzymes. 8,43,44 For instance, recent evidence suggests that 5hmC is likely to be an intermediate in an active de-methylation process in which the first step involves the oxidation of 5mC to 5hmC. It was postulated that 5hmC could get further oxidized to 5-formylcytosine (5fC) or 5-carboxylcytosine (5caC) in a process that involves TET enzymes.…”

“…It was postulated that 5hmC could get further oxidized to 5-formylcytosine (5fC) or 5-carboxylcytosine (5caC) in a process that involves TET enzymes. 9,[43][44][45][46][47][48] 5fC and 5caC can then get excised by and absence/very low expression of the androgen receptor (AR) when cultured under standard cell culture conditions (2D culture) (Fig. 3).…”

Effect of chronic heroin and cocaine administration on global DNA methylation in brain and liver

“…For the reverse process of demethylation, the formation of 5-hydroxymethylcytosine from 5-methylcytosine is required, which is carried out by the ten-eleven translocation proteins (Guo et al, 2011, Dahl et al, 2011. Deaminases convert 5-hydroxymethylcytosine to 5-hydroxymethyluracil which is then repaired to cytosine by the base excision repair pathway (Guo et al, 2011). Methylation of the DNA has been associated with gene silencing, whereas active transcription occurs as a result of demethylation (Franco et al, 2008;Kovatsi et al, 2011;Tang and Ho, 2007).…”

“…The enzymes responsible for the addition of the methyl group are called DNA methyltransferases (DNMT1, 2, 3a and 3b) . For the reverse process of demethylation, the formation of 5-hydroxymethylcytosine from 5-methylcytosine is required, which is carried out by the ten-eleven translocation proteins (Guo et al, 2011, Dahl et al, 2011. Deaminases convert 5-hydroxymethylcytosine to 5-hydroxymethyluracil which is then repaired to cytosine by the base excision repair pathway (Guo et al, 2011).…”

Understanding Ten-Eleven Translocation-2 in Hematological and Nervous Systems

“…In primordial germ cells (PGCs), genome-wide erasure of DNA methylation occurs naturally 42 . It is believed that active DNA demethylation preferentially happens at the specific loci in differentiated somatic cells 43 . 47,48 .…”