Chunk #12 — Introduction — 1. Epigenetic Regulation due to Histone Covalent Modifications — 1A. Role of Histone Acetylation and Deacetylation in Transcriptional Regulation
(Gräff et al., 2012, 2014). Inhibition of HDAC activity may serve as a useful pharmacological approach in the treatment of learning and memory disorders (Fischer, Sananbenesi, Wang, Dobbin, & Tsai, 2007) as HDAC isoform-specific regulation of learning and memory has been demonstrated in both vertebrate and invertebrate models (Fitzsimons, Schwartz, Given, & Scott, 2013; Fitzsimons & Scott, 2011; Guan et al., 2009; Kim et al., 2012; McQuown et al., 2011; Wang, Zang et al., 2011). The class III HDACs, sirtuins, due to their NAD+ dependency, are believed to be critical in the regulation of biological and circadian rhythms, cell survival, metabolic activity, aging and neurodegeneration (Hirayama et al., 2007; Nakahata et al., 2008; Bishop & Guarente, 2007; Cohen et al., 2004; Kim et al., 2007). Dysregulation of the circadian clock has been implicated in psychiatric disorders and alcohol phenotypes in both vertebrate and invertebrate systems (Mansour et al., 2006; Pohl et al., 2013; Sarkar, 2012). Hence HDAC manipulation thereby affecting circadian pathways, could be an important avenue for therapeutic intervention. Recently, the sirtuin isoform SIRT1 has been shown to modulate CREB function and affect learning and memory pathways via its regulation of microRNA-134 (Gao et al., 2010). This serves to
