Complex functions of Gcn5 and Pcaf in development and disease

A wealth of biochemical and cellular data, accumulated over several years by multiple groups, has provided a great degree of insight into the molecular mechanisms of actions of GCN5 and PCAF in gene activation. Studies of these lysine acetyltransferases (KATs) in vitro, in cultured cells, have revealed general mechanisms for their recruitment by sequence-specific binding factors and their molecular functions as transcriptional co-activators. Genetic studies indicate that GCN5 and PCAF are involved in multiple developmental processes in vertebrates, yet our understanding of their molecular functions in these contexts remains somewhat rudimentary. Understanding the functions of GCN5/PCAF in developmental processes provides clues to the roles of these KATs in disease states. Here we will review what is currently known about the developmental roles of GCN5 and PCAF, as well as emerging role of these KATs in oncogenesis. •Gcn5 null embryos are defective in somitogenesis and neurulation, whereas Pcaf null mice show a complete lack of developmental phenotypes.•Hypomorphic mutations that lower Gcn5 levels or abrogate KAT function result in developmental defects such as skeleton defects and exencephaly.•GCN5 is preferably recruited to Myc and E2F1 binding motifs in embryonic stem cells, and multiple Myc and E2F1 targets are affected by Gcn5 loss.•Gcn5 and Pcaf play important roles in both the innate and adaptive immune systems.•GCN5/PCAF KAT activity is linked with the survival of human cancer cell types, however, no clinically useful inhibitor of GCN5/PCAF exist to date.