The Molecular Basis Of Dna Demethylation

DNA methylation is a key epigenetic modification in mammalian genomes and is dynamically regulated in development and diseases. While enzymes catalyzing DNA methylation have been well characterized, those involved in demethylation have remained elusive until recently. Mounting evidence now suggests that the TET proteins, a family of AlkB-like Fe(II)/alpha-ketoglutarate-dependent dioxygenases, initiate active DNA demethylation by oxidizing 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). In this chapter, we discuss the molecular basis of DNA demethylation in mammalian genomes, focusing on TET proteins and TET-mediated oxidative DNA demethylation. Other potential DNA demethylation pathways are also summarized.