Chunk #9 — Introduction — 1. Epigenetic Regulation due to Histone Covalent Modifications — 1A. Role of Histone Acetylation and Deacetylation in Transcriptional Regulation
CBP/p300 are an important family of HATs that act to remodel chromatin architecture functioning as part of different multimeric complexes as well as directly via binding phosphorylated-CREB (cyclic-AMP-response element binding protein). CREB is a critical neuronal transcription factor that regulates normal physiological function and is especially involved in the regulation of the epigenome during alcoholism (Mayr & Montminy, 2001; Starkman et al., 2012). CREB binds to the canonical cAMP responsive element (CRE) consensus sequence at target gene promoters to activate gene expression (Montminy & Bilezikjian, 1987). Phosphorylation at serine 133 serves to activate CREB (pCREB), which recruits the HAT, CBP (Chrivia et al., 1993; Parker et al., 1996), which in conjunction with another protein, p300, mediates chromatin remodeling (Arany, Newsome, Oldread, Livingston, & Eckner, 1995). CBP and p300 have been implicated as targets with therapeutic potential in a variety of neurodegenerative disorders (Valor, Viosca, Lopez-Atalaya, & Barco, 2013). Landmark studies have shown that CBP is important for memory consolidation using a rodent model of Rubinstein-Taybi syndrome (RTS) (Korzus, Rosenfeld, & Mayford, 2004). Mutations in CBP have been shown to impair
