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 modules in the BRD4 protein, a member of the Bromodomain and Extra-Terminal (BET) family [UniProt, Wikipedia]. As an epigenetic reader, BD1 specifically recognizes and binds to acetylated lysine residues on histone tails (such as H4K5ac and H4K8ac) and various transcription factors, facilitating the recruitment of BRD4 to active chromatin regions like enhancers and super-enhancers [NIH, ResearchGate]. This binding is critical for the assembly of the transcriptional elongation complex, involving P-TEFb and the Mediator complex, which drives the expression of genes essential for cell growth, survival, and the inflammatory response [NIH]. In many cancers, including NUT midline carcinoma and acute myeloid leukemia, BRD4 BD1 is a key driver of oncogenic gene expression, particularly the MYC oncogene [Atlas of Genetics and Oncology, NIH]. Small molecule inhibitors targeting BD1, such as JQ1 and clinical-stage pan-BET inhibitors like Birabresib, work by competitively occupying the acetyl-lysine binding pocket, thereby displacing BRD4 from chromatin and suppressing the transcription of its target genes [NIH]. While effective, the use of pan-BET inhibitors is often associated with dose-limiting toxicities such as thrombocytopenia, leading to significant interest in developing BD1-selective inhibitors to achieve a more favorable therapeutic profile [Frontiers in Pharmacology, NIH].

Other names

CAPMCAPCDLS6HUNK1HUNKIFSHRG4Mitotic chromosome-associated proteinBRD4-BD1N-terminal bromodomain 1 of BRD4

Competitive inhibition of acetyl-lysine binding to the bromodomain pocket, preventing BRD4 recruitment to chromatin and subsequent transcriptional activation of target genes [NIH, ResearchGate].