The Bromodomain as an Acetyl-Lysine Reader Domain

Abstract The bromodomain (BrD) is a conserved structural module found in many chromatin-associated proteins that has the ability to recognize acetylated lysine residues on proteins. Bromodomain proteins play fundamental roles in many important cellular processes, ranging from substrate recruitment for histone acetyltransferases to aiding in complex formation at sites of active gene transcription in chromatin. These proteins are typically multi-subunit proteins, in which BrDs and other modular domains work in concert with one another to regulate a complex epigenetic system that ensures highly specific and ordered gene expression. In recent years, small-molecule chemical inhibitors of BrDs have been developed that have helped researchers gain insights into complex mechanisms in chromatin biology and test and validate different BrDs as potential therapeutic targets for new epigenetic therapies. In this chapter, we examine the structure and functions of the BrD, and we provide an overview of its overall role in biology and numerous disease pathways.