p300/CBP genes functions in regulating the expression of genes controlling several basic cellular processes, such as proliferation and homeostasis, and plays a role in a variety of human diseases, particularly solid tumors. Acetylation and deacetylation can be mimicked using site-specific glutamine and arginine mutations (respectively), which preserve the charge of the residue they are replacing but are not substrates for acetyl transfer or deacetylation. A further way in which lysine acetylation is linked to energy balance is through the sirtuin deacetylase enzymes, which require a nicotinamide adenine dinucleotide (NAD) cofactor, and therefore low nutrient conditions can facilitate deacetylation. Bromodomains are domains with the special purpose of binding acetylated proteins, bearing different flanking sequence specificities. Several acetyltransferases have bromodomains, 53 which could mediate further cooperativity between acetylation sites. This has been proposed to influence the histone H4 N-terminal tail acetylation by an an N-terminally progressing zip mechanism. Recent progress has been made toward developing high-throughput assays to measure p300/CBP inhibition against purified enzyme and in cells, screening of natural product and synthetic compound libraries, and developing candidate molecules that could be active in vivo.
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