Bromodomains

The bromodomain family contains an evolutionarily conserved protein fold that specifically binds acetylated lysine residues. This recognition facilitates function by promoting protein-protein interaction. Many bromodomain-containing proteins, such as Type A histone acetyltransferases, are chromatin remodeling enzymes. Other bromodomain-containing proteins act as transcription factors to regulate gene activity.

The human genome encodes more than 50 bromodomain-containing proteins, which can be subdivided into 8 families. These ‘readers’ of the histone code are important regulators of development and normal biological processes. Several key BRD-containing proteins include Brd2 and Brd3, which are associated with MHC recognition, inflammation, and immune response, and Brd4 (also called MCAP), which associates with chromosomes during mitosis. All three BRD proteins have been identified as potential cancer targets. Although a number of bromodomain inhibitors have been developed, including the widely used JQ1, their efficacy in disease states have been limited, highlighting the need for further development of bromodomain inhibitors.