The acetylation of histone lysine residues plays a crucial role in the epigenetic regulation of gene transcription. A bromodomain is a protein domain that recognizes acetylated lysine residues such as those on the N-terminal tails of histones. This recognition is often a prerequisite for protein-histone association and chromatin remodeling. These domains function in the linking of protein complexes to acetylated nucleosomes, thereby controlling chromatin structure and gene expression. Thus, bromodomains serve as “readers” of histone acetylation marks regulating the transcription of target promoters. P300/CBP-associated factor (PCAF) is a transcriptional coactivator that works both as a histone lysine acetyltransferase, through its HAT domain, and as an acetyl-lysine reader through its conserved bromodomain located directly C-terminal to the HAT domain. The PCAF bromodomain binds acetylated histone H3 and H4 as well as non-histone targets. Bromodomain binding is dictated by the position of the acetylated lysine as well as interactions with specific residues flanking the acetyl-lysine. PCAF also specifically binds the HIV viral protein Tat on acetylated K50 to regulate its transactivating activity and help induce chromatin remodeling of proviral genes, thereby promoting transcription of viral proteins.