BET

BET (bromodomain and extraterminal domain) proteins are epigenetic reader proteins that recognize acetylated lysine residues through tandem bromodomains and recruit transcriptional regulatory complexes to chromatin, thereby controlling transcriptional activation and elongation programs^[1][2]. BET family members, including BRD2, BRD3, BRD4, and BRDT, regulate RNA polymerase II-dependent gene expression and are important mediators of enhancer-associated transcriptional networks^[1][3]. Mechanistically, BRD4 functions as a central transcriptional co-regulator by binding acetylated histones and facilitating recruitment of positive transcription elongation factor b (P-TEFb), which promotes productive transcriptional elongation^[2][4]. Dysregulation of BET-dependent transcription has been implicated in cancer, inflammatory disorders, immune-mediated diseases, and viral infection models, where BRD4 contributes to disease-associated gene expression programs^[1][3][5]. Compared with related BET isoforms, BRD4 is the most extensively characterized member and is distinguished by its prominent role in enhancer-driven transcription and broad involvement in oncogenic signaling pathways^[3][6]. For experimental applications, BET bromodomains are highly druggable targets, and small-molecule inhibitors such as JQ1 as well as domain-selective BD1- or BD2-targeting compounds have been widely used to interrogate transcriptional regulation and evaluate therapeutic mechanisms in disease models^[4][7][8]. These pharmacological tools have established BET proteins as key regulators of chromatin-dependent gene expression and valuable targets for mechanistic and translational research^[5][7].