• ANJANA RAO

      Articles written in Journal of Biosciences

    • TET methylcytosine oxidases: new insights from a decade of research

      CHAN-WANG J LIO XIAOJING YUE ISAAC F LO´ PEZ-MOYADO MAMTA TAHILIANI L ARAVIND ANJANA RAO

      More Details Abstract Fulltext PDF

      In mammals, DNA methyltransferases transfer a methyl group from S-adenosylmethionine to the 5 position ofcytosine in DNA. The product of this reaction, 5-methylcytosine (5mC), has many roles, particularly insuppressing transposable and repeat elements in DNA. Moreover, in many cellular systems, cell lineagespecification is accompanied by DNA demethylation at the promoters of genes expressed at high levels in thedifferentiated cells. However, since direct cleavage of the C-C bond connecting the methyl group to the 5position of cytosine is thermodynamically disfavoured, the question of whether DNA methylation wasreversible remained unclear for many decades. This puzzle was solved by our discovery of the TET (Ten-Eleven Translocation) family of 5-methylcytosine oxidases, which use reduced iron, molecular oxygen and thetricarboxylic acid cycle metabolite 2-oxoglutarate (also known as alpha-ketoglutarate) to oxidise the methyl groupof 5mC to 5-hydroxymethylcytosine (5hmC) and beyond. TET-generated oxidised methylcytosines areintermediates in at least two pathways of DNA demethylation, which differ in their dependence on DNAreplication. In the decade since their discovery, TET enzymes have been shown to have important roles inembryonic development, cell lineage specification, neuronal function and cancer. We review these findings anddiscuss their implications here.

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