Epigenetic processes are thought to underlie cross-generational effects of environmental insults, including those related to drugs of abuse (Szutorisz et al, 2014; Vassoler and Sadri-Vakili, 2014). Of the known epigenetic modifications, variation in DNA methylation has been shown both to be mediated by environmental influences and to frequently persist through multiple generations in various organisms (Lange and Schneider, 2010; Becker and Weigel, 2012; Heard and Martienssen, 2014). DNA methylation is central to many key biological processes, is known to colocalize with functional chromatin features (eg, DNaseI hypersensitivity and histone modifications), and has demonstrated effects on gene regulation via interactions with transcription factors and splicing machinery (Cedar and Bergman, 2009; Gutierrez-Arcelus et al, 2015; Hu et al, 2013). With relevance to behavioral and physiological alterations previously described in our model (Szutorisz et al, 2014), DNA methylation has also been widely implicated in normal brain development (Wilson and Sengoku, 2013; Spiers et al, 2015) and psychiatric phenotypes such as anxiety, depression, autism, schizophrenia, bipolar disorder, and addiction (Feng and Nestler, 2013; Schmitt et al, 2014; Tuesta and Zhang, 2014).
