Bromodomain and extraterminal domain protein (BET protein)

The **bromodomain and extraterminal domain proteins** (BET proteins) are a family of conserved transcriptional regulators that act as epigenetic readers by recognizing acetylated lysine residues on histone tails, primarily H3 and H4[1][3][5]. The family comprises four members in humans—BRD2, BRD3, BRD4, and BRDT—distinguished by two N-terminal bromodomains (BD1 and BD2) and a unique extraterminal (ET) domain[5][3][1]. BET proteins play critical roles in organizing chromatin structure, recruiting transcriptional cofactors, and enabling gene expression at promoters and enhancers, especially those characterized as super-enhancers[1][3][5]. They are implicated in a diverse array of biological processes, including cell cycle regulation, inflammation, differentiation, and DNA damage response[6][7]. Aberrant BET protein activity has been linked to cancer, cardiovascular disease, inflammatory disorders, and some viral infections[2][1][5]. Small-molecule inhibitors targeting BET bromodomains—such as JQ1 and I-BET762—disrupt the interaction between BET proteins and acetylated histones, modulating gene transcription in various disease contexts[4][5]. While therapeutically promising, BET inhibition can lead to on-target toxicity and impacts on normal physiological gene regulation[4].

Other names

BET familyBET proteinsbromodomain and extraterminal domain familyBRD2BRD3BRD4BRDT

- Inhibition of BET bromodomain binding to acetylated lysines on histones - Disruption of protein-protein interactions at enhancers and promoters - Blockade of transcription factor recruitment - Suppression of abnormal gene transcription in disease contexts