Bromodomain and extra-terminal domain protein family (BET protein family)

The **Bromodomain and extra-terminal domain protein family** (BET family) consists of four closely related human proteins: BRD2, BRD3, BRD4, and BRDT. BET proteins are characterized by two tandem N-terminal bromodomains (BD1 and BD2), which selectively recognize acetylated lysine residues on histones, and an extra-terminal (ET) domain, which recruits cofactors and modulates a broad spectrum of transcriptional events[1][2][3][5][7]. They act as epigenetic readers, linking chromatin acetylation states to gene expression by recruiting transcription factors, coactivators, the positive transcription elongation factor b (P-TEFb), and other regulatory complexes[2][5][7]. BET proteins play central roles in the regulation of transcription, cell cycle progression, DNA repair, immune responses, and cellular differentiation[1][2][7][9]. Dysregulation of BET proteins (especially BRD4) is implicated in the pathogenesis of various cancers, inflammatory and immune diseases, and viral infections, making them valuable therapeutic targets. Numerous BET inhibitors (e.g., JQ1, OTX015) are being clinically investigated for the treatment of cancers and inflammation by interfering with BET-acetylated chromatin interactions and downregulating key pathogenic gene programs[5][7][9].

Other names

BET familyBET proteinsBRD2/BRD3/BRD4/BRDT subfamilyBromodomain and extraterminal motif proteins

Competitive inhibition of bromodomain–acetyl-lysine interactions; Transcriptional repression of oncogenic and inflammatory genes; Disruption of chromatin-protein complex formation