Abstract
DNA modifications provide attractive regulatory mechanisms for the long-lasting changes in transcription that contribute to the behavioral abnormalities characteristic of drug addiction. Although methylcytosine has been the most studied DNA epigenetic modification, recent studies have identified methylcytosine oxidation and additional forms of altered DNA. These findings have demonstrated the complexity of DNA modifications and opened new avenues for future research. Here, we summarize the accumulating evidence for DNA methylcytosine and its catalyzing enzymes, DNA methyltransferases, in addiction, as well as the emerging role of methylcytosine oxidation and the related Ten-eleven translocation family of dioxygenases. In addition, we review recent progress in the genome-wide profiling of these modifications in brain and peripheral tissues and highlight current challenges and future directions. Unraveling the functional relevance of these epigenetic mechanisms in addiction is adding to our understanding of this syndrome, which has the potential to prompt novel approaches for better diagnosis and therapy.
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