bromodomomen

Bromodomains are small protein motifs of about 110 amino acids that function as epigenetic readers by recognizing acetylated lysine residues, most notably on histone tails. By binding acetyl-lysine marks, they help translate chromatin states into changes in gene expression and chromatin architecture. The interaction is mediated by a conserved asparagine that forms a hydrogen bond with the acetyl group and by a hydrophobic pocket formed by a left-handed bundle of four alpha helices.

Bromodomains occur in a wide range of chromatin-associated proteins across eukaryotes. In humans there are roughly 60 bromodomains housed in about 50 proteins. The best-characterized group is the bromodomain and extraterminal (BET) family, which includes BRD2, BRD3, BRD4, and BRDT. Other examples include BRWD1, BRD7, BRD9, and tandem bromodomains found in certain chromatin remodelers such as ATAD2. Bromodomains can recognize various acetylation marks, and their binding is influenced by the surrounding chromatin context and interacting partners.

Functionally, bromodomains help recruit transcriptional machinery and chromatin-modifying complexes to acetylated regions, thereby promoting transcription initiation and elongation, enhancer–promoter communication, and, in some contexts, DNA damage responses. They act as molecular readers that couple histone modification status to downstream gene regulatory outcomes.

Clinically, bromodomain activity is a target for therapeutic intervention. Small-molecule inhibitors, particularly those targeting BET bromodomains (for example, JQ1 and related compounds), have been explored in cancer, inflammatory diseases, and fibrosis. Development focuses on achieving selective modulation while managing potential on-target and off-target effects.