Bromodomain and PHD Finger-Containing Protein 1: From Functions to a Developmental Disorder, Cancer, and Therapeutics

Bromodomain and PHD finger-containing protein 1 (BRPF1) is an essential epigenetic regulator and plays a key role in post-translational modification of histones. It is a chromatin reader that recognizes acetylated histones and interacts with the paralogous lysine acetyltransferases KAT6A and KAT6B to promote histone acetylation and related acylations, such as propionylation, at lysine 23 of histone H3, thereby influencing gene expression and regulating developmental programs. BRPF1 contributes to a variety of cellular processes such as cell cycle progression, cell proliferation, cell differentiation, and responses to cellular stresses, including DNA damage. Moreover, BRPF1 is implicated in hematopoiesis, embryonic development, skeletal development, neurodevelopment, neurogenesis, learning, and memory. BRPF1 gene knockout in mice leads to severe bone marrow failure, anemia, and eventual death in a few weeks after birth. This review provides a brief overview of BRPF1 and its contribution to the molecular structure and biological functions of KAT6A and KAT6B complexes. We will explore the emerging evidence linking BRPF1 dysfunction to human diseases, particularly cancer and abnormal neurodevelopment, to highlight promising therapeutic opportunities for treating associated pathology.