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Chunk #2 — Introduction

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Epigenetic mechanisms in alcohol- and adversity-induced developmental origins of neurobehavioral functioning.
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Changes to chromatin structure can occur at many levels. DNA methylation, the addition of methyl groups to cytosines in DNA, is one of the most studied epigenetic modifications in terms of developmental alcohol or stress exposure. Methylation often represses gene transcription (Jones and Takai, 2001) (as depicted in Figure 1), though this effect is dependent on cytosine location in the genome (Guibert and Weber, 2013). Methyl groups are added to DNA via DNA methyltransferases (DNMT1, 3A, DNMT3B, and DNMT3L), which are differentially expressed throughout development (Okano et al., 1999). DNMT1 is typically associated with maintenance of methyl marks carried through replication or “cell memory,” while DNMT3A and 3B are essential for de novo methylation (Okano, 1999). DNMT3L has been less well-studied, but has been to act through suppression of inherited maternal methylation marks and stimulation of DNMT3A activity (Bourc'his et al., 2001; Hata et al., 2002). Active demethylation of DNA can occur through hydroxymethylation, with the formation of 5-hydroxymethylcytosine (5-hmC) catalyzed by the ten-eleven translocation methylcytosine dioxygenase (TET) family of enzymes (Guibert and Weber, 2013). It should be noted that