Bromodomain and extraterminal domain family protein (BET protein)

Bromodomain and extraterminal domain family proteins (BET proteins; BRD2, BRD3, BRD4, and BRDT) are evolutionarily conserved epigenetic readers characterized by two N-terminal bromodomains and an ET (extraterminal) domain. BET proteins recognize acetylated lysine residues primarily on histone tails, mediating the recruitment of transcriptional regulators and RNA polymerase II, and thereby activating transcription elongation and gene expression. They play essential roles in regulating cell cycle, proliferation, DNA damage repair, and immune responses. Dysfunction or dysregulation of BET proteins is linked to cancer, inflammation, and other disease states, making them prominent therapeutic targets. Several small-molecule inhibitors targeting BET bromodomains are in development or clinical testing, offering new avenues for the treatment of cancer and inflammatory diseases by modulating aberrant epigenetic and transcriptional programs.

Other names

BET familyBET proteinsBromodomain and extraterminal familyBRD2/BRD3/BRD4/BRDT (when referencing individual members)

Competitive inhibition of bromodomains: Small molecules such as JQ1 and I-BET151 bind to the acetyl-lysine recognition pocket of BET proteins, blocking their interaction with acetylated histones, leading to suppression of transcription programs involved in disease (particularly oncogenic transcription).