Bromodomain-containing protein 4, bromodomain 1 (BRD4-BD1) (BRD4-BD1)

Bromodomain-containing protein 4, bromodomain 1 (BRD4-BD1) is the first of two highly conserved N-terminal bromodomains in the BRD4 protein, a key member of the Bromodomain and Extra-Terminal (BET) family [3, 15]. As an epigenetic reader, BRD4-BD1 specifically recognizes and binds to acetylated lysine residues on histone tails, particularly the diacetylated H4K5AcK8Ac mark, which anchors the protein to chromatin [3, 6]. This binding facilitates the recruitment of the Mediator complex and the positive transcription elongation factor b (P-TEFb), thereby driving the expression of genes essential for cell cycle progression and growth, such as MYC [1, 10]. Dysregulation of BRD4-BD1 is implicated in various pathologies, including NUT midline carcinoma, acute myeloid leukemia, and chronic inflammatory diseases [8, 13]. Pharmacological targeting of this domain with small-molecule inhibitors like JQ1 or BD1-selective agents like MS436 aims to disrupt these protein-protein interactions, leading to the downregulation of oncogenic and pro-inflammatory transcriptional programs [11, 17]. Clinical development of such inhibitors faces challenges including dose-limiting toxicities like thrombocytopenia and the emergence of resistance mechanisms [2, 14].

Other names

BRD4MCAPHUNK1HUNKICAPCDLS6FSHRG4Chromosome-associated proteinMitotic chromosome-associated protein

Competitive inhibition of acetyl-lysine binding to the bromodomain pocket, which displaces the protein from chromatin and prevents the recruitment of transcriptional machinery to oncogenic and inflammatory gene loci.