Bromodomain-containing protein 4 (BRD4) (BRD4)

Bromodomain-containing protein 4 (BRD4) is a chromatin reader protein encoded by the BRD4 gene that recognizes acetylated lysine residues on histones H3 and H4 via its two bromodomains (BD1 and BD2), facilitating epigenetic memory transmission across cell divisions.[1][4][8] As a member of the BET family, BRD4 recruits transcription elongation factor P-TEFb and RNA polymerase II to promoters and superenhancers, driving gene expression for cell cycle progression, mitosis, and inflammatory responses.[1][4][5] It possesses intrinsic kinase activity to phosphorylate RNA Pol II CTD at Ser2 for transcription elongation and histone acetyltransferase (HAT) activity to decondense chromatin and reduce nucleosome occupancy at target genes like Myc and Fos.[4] BRD4 plays pivotal roles in diseases including cancer (e.g., NUT midline carcinoma, leukemia, lymphoma), cardiovascular conditions (e.g., hypertrophy, ischemic heart disease), and inflammation (e.g., IBD via NF-κB stabilization).[1][2][3][4] Therapeutically, BRD4 is targeted by BET inhibitors like JQ1, which disrupt its chromatin binding to suppress tumor growth, cytokine production, and fibrosis without overt toxicity in preclinical models.[3][7]

Other names

BRD4BET proteinMCAP homolog

Bromodomain inhibition (disrupts binding to acetylated histones), Suppression of NF-κB activity, Inhibition of P-TEFb recruitment, Blockade of superenhancer activity, Reduction of inflammatory cytokine expression