Bromodomain-containing protein 4 (BRD4-BD1) (BRD4-BD1)

Bromodomain-containing protein 4 (BRD4) bromodomain 1 (BD1) is the N-terminal epigenetic reader domain of the BRD4 protein, a member of the Bromodomain and Extra-Terminal (BET) family [1, 2]. It functions by recognizing and binding to acetylated lysine residues on histone tails, specifically the H4K5AcK8Ac motif, thereby anchoring BRD4 to chromatin to facilitate transcriptional activation and elongation [1, 4, 7]. BRD4-BD1 is essential for the recruitment of the positive transcription elongation factor b (P-TEFb) and the regulation of growth-promoting genes such as MYC [7, 14]. Dysregulation of BRD4-BD1-mediated transcription is a hallmark of various cancers, including acute myeloid leukemia and NUT midline carcinoma, and plays a significant role in inflammatory and cardiovascular diseases [2, 4, 11, 13]. Therapeutic strategies targeting this domain include small-molecule inhibitors and proteolysis-targeting chimeras (PROTACs) that competitively block the acetyl-lysine binding pocket, leading to the suppression of oncogenic and pro-inflammatory gene expression [4, 9, 12]. While pan-BET inhibitors target both BD1 and BD2, domain-selective inhibitors are being developed to improve the therapeutic index and reduce side effects like thrombocytopenia [4, 14, 15].

Other names

HUNK1MCAPBromodomain-containing protein 4, N-terminal bromodomainBET protein 4

Competitive inhibition of the acetyl-lysine binding pocket, which prevents the recruitment of BRD4 to chromatin and disrupts the assembly of transcriptional complexes like P-TEFb.