Chunk #11 — Introduction — 1. Epigenetic Regulation due to Histone Covalent Modifications — 1A. Role of Histone Acetylation and Deacetylation in Transcriptional Regulation
Generally, as discussed above, transcriptional activators and co-activators recruit HATs such as CBP, whereas repressors and co-repressors recruit HDACs. HDACs reverse the activity of HATs and cause a decrease in transcription through removal of acetyl groups from histones. HDACs are grouped into four classes: class I HDACs (1,2,3 and 8), class II HDACs (4,5,6,7 and 9) and class IV HDACs are similar in that they require zinc for activity whereas class III HDACs or sirtuins are structurally unique requiring NAD+ for enzymatic activity (Blander & Guarente, 2004; Haberland, Montgomery, & Olson, 2009). Regulating the amount of histone acetylation by manipulating HDAC activity is an attractive therapeutic option for treating brain disorders. HDAC2 appears to be an important molecule in maintaining normal neuronal cognitive function and regulating hippocampal memory with implications for remote fear memory and treatment of post-traumatic stress disorders (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
