Bromodomain

A bromodomain is a conserved protein motif of about 110 amino acids that recognizes acetylated lysine residues, most notably on histone tails. As an epigenetic reader module, bromodomains help interpret histone acetylation marks to regulate chromatin structure and gene expression.

Structurally, bromodomains form a four-helix bundle with ZA and BC loops creating a hydrophobic pocket that binds acetyl-lysine. A conserved asparagine residue coordinates the acetyl group, enabling selective recognition of specific acetylation marks and contributing to the affinity and specificity of binding.

Bromodomain-containing proteins are often present in families such as the BET proteins BRD2, BRD3, BRD4 and BRDT, as well as BRD7, BRD9, and BRPF factors. They function as transcriptional regulators by recruiting chromatin modifiers and transcriptional machinery to acetylated chromatin regions, thereby influencing gene expression and chromatin dynamics. They can participate in processes including transcriptional activation, chromatin remodeling, and DNA damage responses.

In biology and medicine, bromodomains are studied as epigenetic targets. Small-molecule inhibitors of bromodomains, notably BET inhibitors such as JQ1, disrupt acetyl-lysine binding and affect transcription of genes associated with oncogenesis and inflammation. These inhibitors are investigated for cancer, inflammatory diseases, and viral infections, among other applications.

Ongoing research aims to map the specificity of individual bromodomains, understand non-histone acetylation recognition, and develop selective therapeutics. Structural and chemical biology approaches continue to illuminate bromodomain-dependent regulatory networks and their roles in health and disease.