Bromodomain and Extra-Terminal Domain (BET) protein family (BET)

The Bromodomain and Extra-Terminal Domain protein family consists of four chromatin-associated proteins—BRD2, BRD3, BRD4, and BRDT—that specifically recognize acetylated lysine residues on histone tails via their tandem bromodomains. Acting as epigenetic "readers," they regulate gene transcription, chromatin architecture, and the recruitment and elongation of RNA polymerase II, impacting processes such as cell cycle progression, proliferation, differentiation, immune response, and development. BET proteins are essential for normal cell function and play diversely specialized roles—including testis-specific functions for BRDT, and key roles in embryogenesis and metabolic regulation for BRD2. Aberrant function or overexpression of BET proteins—especially BRD4—has been implicated in oncogenesis, inflammation, viral latency, and other diseases. They are therapeutically actionable targets, with several pan-BET inhibitors currently in clinical and preclinical development.

Other names

BETBET proteins

Competitive inhibition of bromodomain binding to acetylated lysines in histones, thereby blocking recruitment of transcriptional co-activators and repressing expression of BET-dependent genes (such as MYC). Specific disruption of chromatin association leads to reduced transcriptional activity of proliferation-promoting genes.