Other chromatin modifications can alter gene activity, including histone acetylation and trimethylation (Figure 1). Histone acetylation loosens chromatin to make DNA more accessible to transcription factors (Grunstein, 1997; Struhl, 1998). In terms of histone methylation, downstream effects on gene regulation depend largely on the specific amino acid modified. For example, trimethylation of Histone 3 lysine 4 (H3K4me3) is associated with activated transcriptional activity, while trimethylation of other lysine residues is associated with transcriptional repression. Beyond modifications to individual amino acids, chromatin accessibility is controlled through complex combinations of modifications to histone tails (Jenuwein and Allis, 2001). Specialized protein domains recognize each combination and are directed to alter chromatin organization. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), are additional pathways through which prenatal alcohol exposure (PAE) and stress can alter protein synthesis (Figure 1). Mature miRNAs are fragments of RNA cleaved from primary miRNA (pri-miRNA) by the enzyme Dicer (He and Hannon, 2004). These mature miRNAs silence gene expression either by preventing translation of mRNA into protein or by speeding up degradation of the mRNA. Other ncRNAs have important biological roles as well, including RNA splicing and DNA replication (Mercer et al., 2009).
