Bromodomain-containing protein 4, first bromodomain (BRD4-BD1)

Bromodomain-containing protein 4, first bromodomain (BRD4-BD1) is a critical epigenetic reader domain within the BRD4 protein, a member of the Bromodomain and Extra-Terminal (BET) family. It functions by recognizing and binding to acetylated lysine residues on histone tails, particularly the di-acetylated H4K5AcK8Ac motif, which anchors BRD4 to specific chromatin regions like super-enhancers. Once bound, BRD4 recruits the positive transcription elongation factor b (P-TEFb) and other co-activators to stimulate the transcription of genes involved in cell cycle progression and growth. In various diseases, especially cancers like NUT midline carcinoma and acute myeloid leukemia, BRD4-BD1 drives the aberrant expression of oncogenes such as MYC. Small-molecule inhibitors like JQ1 and OTX015 target this domain by competitively occupying the acetyl-lysine binding pocket, thereby displacing BRD4 from chromatin and inducing apoptosis in malignant cells. Beyond oncology, BRD4-BD1 is a target for treating chronic inflammation and viral infections by modulating the expression of pro-inflammatory cytokines and viral genes. However, therapeutic inhibition of this domain is associated with clinical challenges, including dose-limiting thrombocytopenia and gastrointestinal toxicities.

Other names

BRD4-BD1HUNK1MCAPFshrg4Mitotic chromosome-associated protein

Competitive inhibition of acetyl-lysine binding in the bromodomain hydrophobic pocket, displacing the protein from chromatin and suppressing downstream gene transcription.