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

Bromodomain-containing protein 4 (BRD4) is a key member of the Bromodomain and Extra-Terminal (BET) family, functioning as an epigenetic reader that recognizes acetylated lysine residues on histone tails [UniProt: P21333]. It contains two highly conserved N-terminal bromodomains, BD1 and BD2, which are essential for its recruitment to chromatin and its role in regulating gene expression. BD1 is primarily responsible for the initial recognition of acetylated histones, facilitating the recruitment of the Positive Transcription Elongation Factor b (P-TEFb) complex to promote RNA polymerase II-dependent transcription [PubMed: 24847884]. In various diseases, particularly cancers like NUT midline carcinoma and acute myeloid leukemia, BRD4 is often overexpressed or dysregulated, driving the transcription of potent oncogenes such as MYC [PubMed: 21885469]. Therapeutic strategies involve small molecule inhibitors that competitively bind to the acetyl-lysine binding pocket of BD1, thereby displacing BRD4 from chromatin and inhibiting the expression of pro-survival and pro-proliferative genes [PubChem: BRD4]. While many clinical-stage inhibitors target both BD1 and BD2, research into BD1-selective inhibitors like GSK778 is ongoing to optimize efficacy and minimize the systemic toxicities often associated with pan-BET inhibition [PubMed: 32193348].

Other names

BRD4 BD1Bromodomain-containing protein 4 N-terminal bromodomainHUNK1MCAP

Competitive inhibition of acetylated lysine binding to the bromodomain pocket, leading to displacement of BRD4 from chromatin and subsequent suppression of target gene transcription [PubMed: 24847884].