Local chromatin microenvironment determines DNMT activity : from DNA methyltransferase to DNA demethylase or DNA dehydroxymethylase

摘要: Insights on active DNA demethylation disproved the original assumption that methylation is a stable epigenetic modification. Interestingly, mammalian methyltransferases 3A and 3B (DNMT-3A -3B) have also been reported to induce demethylation, in addition their well-known function catalyzing methylation. In situations of extremely low levels S-adenosyl methionine (SAM), DNMT-3A -3B might demethylate C-5 methyl cytosine (5mC) via deamination thymine, which subsequently replaced by an unmodified through base excision repair (BER) pathway. Alternatively, 5mC when converted 5- hydroxymethylcytosine (5hmC) TET enzymes, be further modified under oxidized redox conditions, although exact pathways are yet elucidated. even direct conversion catalyzed DNMTs. Here, we summarize evidence dehydroxymethylase demethylase activity -3B. Although physiological relevance needs demonstrated, current indications 5mC- 5hmC-modifying activities de novo shed new light these enzymes. Despite extreme circumstances required for such unexpected reactions occur, here put forward chromatin microenvironment can locally exposed hypothesize waves extremes allow enzymes act differential ways.