Bromodomain-containing protein 4, second bromodomain (BRD4 BD2)

Bromodomain-containing protein 4, second bromodomain (BRD4 BD2) is a specialized epigenetic reader domain that plays a critical role in the regulation of gene transcription. As a member of the BET family, BRD4 contains two tandem bromodomains, with BD2 specifically facilitating the recruitment of the positive transcription elongation factor b (P-TEFb) to promote the transition of RNA polymerase II into productive elongation. This process is vital for the expression of key oncogenes and pro-inflammatory mediators, such as MYC and various cytokines. In disease states like cancer and chronic inflammation, BRD4 BD2 is often hijacked to maintain pathological gene expression programs. Small-molecule inhibitors targeting BD2 are designed to disrupt these interactions, offering a therapeutic strategy for malignancies and cardiovascular conditions. Recent drug development has focused on BD2-selective inhibitors to improve the therapeutic window and reduce systemic toxicities, such as thrombocytopenia, which are commonly associated with non-selective pan-BET inhibition.

Other names

BRD4-BD2Bromodomain 2 of BRD4HUNK1MCAPBromodomain-containing protein 4, domain 2

Competitive inhibition of the acetyl-lysine binding pocket within the second bromodomain of BRD4, preventing the recruitment of P-TEFb and other transcriptional machinery to chromatin.