Bromodomainproteine

Bromodomain-containing proteins, or bromodomain proteins (BRD proteins), are a family of chromatin-associated proteins that read epigenetic marks by means of bromodomains. A bromodomain is a ~110 amino acid motif that forms a hydrophobic pocket capable of recognizing acetylated lysine residues on histone tails. Binding typically occurs to acetylated lysines such as H3K27ac or H4K5ac, thereby linking histone acetylation to the recruitment of transcriptional regulators and chromatin remodelers.

BRD proteins participate in gene regulation, chromatin remodeling, DNA repair, and cell cycle control. They commonly act as scaffolds or recruiters for complexes that promote transcription initiation and elongation, or for chromatin-modifying enzymes. The best-studied subfamily is the BET proteins—BRD2, BRD3, BRD4, and BRDT—that regulate transcriptional programs through interactions with P-TEFb and enhancers, including super-enhancers, and are implicated in cancer and developmental processes.

Beyond BET, numerous BRD proteins exist, such as BRD7, BRD9, BRPF1-3, ATAD2, ZMYND11, and others. These factors have diverse domain architectures that determine chromatin localization and functional output, ranging from transcriptional activation to repression and chromatin remodeling.

Because aberrant reading of histone acetylation can drive disease, bromodomain proteins are active targets for drugs. Small-molecule bromodomain inhibitors, notably those targeting BET family members (e.g., JQ1, OTX015), have shown preclinical activity and reached early clinical trials for cancer and inflammatory diseases. Other BRD inhibitors are under investigation. Potential adverse effects, resistance, and selectivity remain areas of study.