Chunk #8 — Introduction — 1. Epigenetic Regulation due to Histone Covalent Modifications — 1A. Role of Histone Acetylation and Deacetylation in Transcriptional Regulation
One of the well-characterized histone covalent modifications is lysine acetylation and its opposing mark deacetylation, which are facilitated by two groups of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). Histone acetylation helps neutralize the basic charge of lysine by directly promoting the unraveling of DNA through minimizing nucleosomal contacts (Bannister & Kouzarides, 2011). HATs are associated with transcriptional initiation and elongation, genome stability and cell cycle-regulated DNA repair (Masumoto, Hawke, Kobayashi, & Verreault, 2005; Wang et al., 2009). Gene activation is enabled through acetylation of specific lysine tails predominantly located on the N- termini of core histones (H2A, H2B, H3 and H4) resulting in an increase in transcription. Numerous lysine residues undergo acetylation including K5, K8, K12, K16 in histone H4 and K9, K14, K18 and K56 in histone H3 (Allis et al., 2007). The three major families of HATs are: the GNAT family (Gcn5-associated N-acetyltransferase) which include Gcn5, PCAF and others; the MYST family (named after its founding members MOZ, Ybf2/Sas3, Sas2, Tip60) and the global co-activators CREB binding protein/p300 (CBP/p300) family (Sterner & Berger, 2000). (Figure 1)
