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Home arrow Health arrow DNA Modifications in the Brain. Neuroepigenetic Regulation of Gene Expression
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Epigenetic Modifications of DNA and Drug Addiction

J. Feng, E.J. Nestler

Icahn School of Medicine at Mount Sinai, New York, NY, United States

INTRODUCTION

DNA methylation is an epigenetic mechanism in which a methyl group is covalently coupled to the C-5 position of cytosine, predominantly at CpG dinucleotides (Jaenisch & Bird, 2003). It is catalyzed by a group of enzymes called DNA methyl- transferases (DNMTs), which include the maintenance enzyme DNMT1 and the de novo DNA methyltransferases DNMT3a and DNMT3b. The role of DNA methyla- tion has been widely demonstrated by its involvement in genomic imprinting (silencing of germline specific genes in somatic cells), retroviral silencing, and X chromosome inactivation. These phenomena arise early in development and affect all tissues and cell types.

The role of DNA methylation in the nervous system has unique features because the brain is composed predominantly of postmitotic neurons and slowly dividing glia cells. Accumulating evidence has implicated DNA methylation in neural plasticity, learning and memory, and cognition (Day & Sweatt, 2011; Lubin, Gupta, Parrish, Grissom, & Davis, 2011; Mikaelsson & Miller, 2011; Moore, Le, & Fan, 2013; Nelson & Monteggia, 2011; Shin, Ming, & Song, 2014). Being an aberrant form of neural plasticity (Hyman, Malenka, & Nestler, 2006), drug addiction also has been shown to be mediated, in part, via several forms of epigenetic regulation, such as histone acetylation and methylation, and by noncoding RNA (Feng & Nestler, 2013; Godino, Jayanthi, & Cadet, 2015; Kenny, 2014; Kyzar & Pandey, 2015; LaPlant & Nestler, 2011; Maze & Nestler, 2011; Nielsen, Utrankar, Reyes, Simons, & Kosten, 2012; Ponomarev, 2013; Robison & Nestler, 2011; Rogge & Wood, 2013; Schmidt, McGinty, West, & Sadri-Vakili, 2013; Starkman, Sakharkar, & Pandey, 2012; Walker, Cates, Heller, & Nestler, 2015). However, studies of DNA methylation in addiction are still relatively few in number. Here, we review the literature on DNA methylation and novel forms of DNA modification in addiction, with a focus on cocaine and ethanol, the two drugs of abuse most studied at this level of analysis to date.

Copyright © 2017 Elsevier Inc.

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DNA Modifications in the Brain ISBN 978-0-12-801596-4

http://dx.doi.org/10.1016/B978-0-12-801596-4.00008-3

 
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