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

Bromodomain and extra-terminal domain family proteins (BET proteins) are a group of epigenetic readers that bind specifically to acetylated lysine residues on histone tails through their tandem bromodomains, thereby regulating chromatin structure and gene transcription[1][2][5][6]. The mammalian family comprises BRD2, BRD3, BRD4, and BRDT, all characterized by highly conserved N-terminal bromodomains (BD1 and BD2) and an extra-terminal domain, with BRD4 and BRDT additionally featuring a C-terminal domain involved in recruiting transcriptional machinery[2][6]. BET proteins play crucial roles in cell proliferation, differentiation, inflammation, and are instrumental in the development and maintenance of multiple diseases, notably cancer and viral infections[1][2][5][6]. Small molecule inhibitors of BET proteins interfere with the protein's ability to recognize acetylated lysine, selectively repressing oncogenic transcriptional programs such as c-MYC, and are under clinical investigation for cancer and other indications[1][2][5]. BRDT is notable for its restriction to testis and a critical role in spermatogenesis; loss of function can result in infertility[6].

Other names

BET protein familyBromodomain and extraterminal domain proteinsBRD2, BRD3, BRD4, BRDT (family members)

Inhibition of bromodomain-acetyl lysine interaction. Blocking BET recruitment to chromatin. Repression of c-MYC and other oncogenic transcriptional networks. Interference with recruitment of P-TEFb and transcriptional elongation.