Bromodomain-containing protein 2, Bromodomain-containing protein 3, Bromodomain-containing protein 4, and Bromodomain testis-specific protein (BRD2, BRD3, BRD4, BRDT)

The BET (Bromodomain and Extra-Terminal domain) family includes four human proteins—BRD2, BRD3, BRD4, and BRDT—which function as epigenetic readers by recognizing acetylated lysine residues on histones and transcription factors[3][4][5]. Structurally, they contain two N-terminal bromodomains and an extra-terminal (ET) domain, and, in the case of BRDT, a PEST motif[1][2][3][5]. BET family proteins regulate gene transcription by recruiting regulatory complexes to chromatin, playing vital roles in cell cycle control, genome organization, spermatogenesis (BRDT), immune modulation, and oncogenesis[1][3][4][5]. Aberrant expression, mutation, or fusion of BET proteins is implicated in aggressive cancers, especially NUT midline carcinoma (BRD4/BRD3-NUT fusions), as well as inflammation, renal disease, cardiovascular disease, and male infertility[1][2][4][5]. Drugs that inhibit BET bromodomains (BET inhibitors) block the ability of these proteins to read acetylation marks and suppress transcription of disease-driving genes, making BET proteins important therapeutic targets under active clinical and preclinical investigation[1][4][5][6].

Other names

BET family proteinsBromodomain and extra-terminal domain proteinsRING3 protein familyMCAP

Inhibitors block acetyl-lysine recognition by BET bromodomains, preventing binding to chromatin and regulatory proteins, thereby suppressing transcription of disease-driving genes and oncogenes. Induction of spermatogenic arrest by blocking BRDT chromatin interactions (male contraception).