Bromodomain and PHD finger-containing protein 1 (BRPF1)

Bromodomain and PHD finger-containing protein 1 (BRPF1) is a multivalent chromatin regulator and scaffolding protein found in the nucleus and encoded by the BRPF1 gene (chromosome 3p25 in humans). BRPF1 contains two plant homeodomain (PHD) fingers, one bromodomain, and a PWWP domain, which allow it to selectively recognize and bind various epigenetic marks and acetylated lysines on histones. BRPF1 is an essential subunit in several histone acetyltransferase (HAT) complexes—most notably the MOZ/MORF and HBO1 complexes—where it stimulates HAT enzymatic activity and helps target H3K14, H3K23, and other lysines for acetylation. It acts as a master regulator of gene expression, regulating genes such as RUNX1, RUNX2, EZH2, and E2F2. BRPF1 is indispensable for embryonic and neurodevelopment, hematopoiesis, and chromatin organization. Mutations or upregulation of BRPF1 are associated with neurodevelopmental disorders, intellectual disability, facial dysmorphism, and several cancers (notably HCC, leukemia, and medulloblastoma). In cancer, BRPF1 promotes cell proliferation, stemness, and tumorigenicity, making it a validated therapeutic target, with inhibitors such as GSK5959 under investigation. Targeting BRPF1 is complicated by its essential roles in development and normal cell function, raising concerns about therapeutic specificity and safety.

Other names

PeregrinBR140Protein Br140bromodomain-containing protein 140kDIDDDFPBRPF1ABRPF1B

Inhibition of bromodomain binding to acetylated lysines; Suppression of histone acetyltransferase activity through complex disruption; Downregulation of cell proliferation and cancer stemness gene expression