Drugs of abuse and epigenetics: Past, present and future.

carbon in the cytosine base (5-mC), catalyzed by DNA methyltransferases (e.g., DNMT1, DNMT3a, DNMT3b), which mainly occurs in the CpG dinucleotides within the genome, and that is often associated with the repression of transcription (Kouzarides, 2007). Histone modifications relate to post-translational changes (e.g., acetylation, methylation, phosphorylation) in the amino acid residues of these proteins, which can cause transcriptional activation, silencing, and chromatin assembly. For example, histone acetyl transferases catalyze the addition of acetyl groups, usually on a lysine (K) residue, causing chromatin relaxation, which promotes a transcriptionally accessible state. Histone methylation may cause either gene activation or repression, depending on where it occurs. For example, promoter methylation may silence gene expression, whereas methylation occurring at another site of the DNA sequence may trigger the expression of a different gene (D’Addario et al., 2013). Noncoding RNAs (e.g., miRNAs) comprise a family of small RNAs that post-transcriptionally regulate gene expression in a negative manner, controlling processes like chromosome dynamics, RNA editing or mRNA degradation (Korolev et al., 2018; Liu et al., 2018). Epigenetic changes