Bromodomain and PHD finger-containing protein 2 (BRPF2)

Bromodomain and PHD finger-containing protein 2 (BRPF2), also known as BRD1, is a key epigenetic reader and scaffold protein within the BRPF family [1, 2, 11]. It plays a fundamental role in regulating gene expression by assembling and directing the HBO1 (KAT7) histone acetyltransferase (HAT) complex to specific chromatin sites [2, 11, 12]. Through its bromodomain, BRPF2 recognizes acetylated lysine residues on histones H3, H4, and H2A, which facilitates the acetylation of histone H3 at lysine 14 (H3K14), a mark associated with active transcription [2, 11, 12, 13, 14]. This process is particularly vital for erythropoiesis, as BRPF2-mediated recruitment of HBO1 is required for the expression of erythroid regulator genes like Gata1 [3, 11]. In clinical contexts, BRPF2 is linked to several pathologies; its dysregulation is observed in various cancers, including leukemia and solid tumors, where it may drive oncogenic transcriptional programs [1, 3, 8, 9]. Furthermore, genetic variations in BRPF2 have been associated with neurodevelopmental and psychiatric disorders such as schizophrenia and bipolar disorder [2, 7, 11]. Therapeutic interest in BRPF2 has led to the development of small-molecule inhibitors like BAY-299, which target its bromodomain to disrupt chromatin binding and gene activation [3, 5, 6, 8]. However, because BRPF2 is essential for normal development and hematopoiesis, pharmacological inhibition poses risks of systemic toxicities, most notably severe anemia and developmental defects [2, 3, 11, 12].

Other names

BRD1Bromodomain-containing protein 1

Bromodomain inhibition [1, 5], preventing recruitment of the HBO1 histone acetyltransferase complex to chromatin [1, 11, 12] and suppressing gene transcription [1, 11].