Targeting lysine acetylation readers and writers

Abstract

Lysine acetylation is a major post-translational modification in histones and other proteins that is catalysed by the ‘writer’ lysine acetyltransferases (KATs) and mediates interactions with bromodomains (BrDs) and other ‘reader’ proteins. KATs and BrDs play key roles in regulating gene expression, cell growth, chromatin structure, and epigenetics and are often dysregulated in disease states, including cancer. There have been accelerating efforts to identify potent and selective small molecules that can target individual KATs and BrDs with the goal of developing new therapeutics, and some of these agents are in clinical trials. Here, we summarize the different families of KATs and BrDs, discuss their functions and structures, and highlight key advances in the design and development of chemical agents that show promise in blocking the action of these chromatin proteins for disease treatment.