BRPF3

BRPF3 (bromodomain and PHD finger-containing protein 3) is a chromatin-associated scaffold protein that functions within the HBO1/KAT7 histone acetyltransferase complex and contributes to the regulation of DNA replication initiation through histone modification mechanisms^[1]. Mechanistically, BRPF3 directs HBO1 substrate specificity toward histone H3 lysine 14 acetylation (H3K14ac), resulting in enrichment of BRPF3, HBO1, and H3K14ac at ORC1-binding sites and replication origins located near transcription start sites^[1]. This chromatin-regulatory activity promotes efficient replication origin activation, as BRPF3 depletion reduces H3K14 acetylation at selected origins and impairs CDC45 recruitment required for origin firing^[1]. Therefore, BRPF3 represents an important epigenetic regulator linking histone acetylation, replication origin activation, and genome duplication programs^[1]. In experimental models, BRPF3 deficiency decreases replication origin activation while preserving MCM2-7 loading, supporting a specific role in origin activation rather than replication licensing^[1]. Compared with the related paralogs BRPF1 and BRPF2, BRPF3 forms a functional HBO1-containing complex with distinct biological properties and is not required for mouse development or survival, indicating functional divergence within the BRPF family^[2]. This isoform-specific activity makes BRPF3 particularly useful for studies investigating chromatin-dependent replication control and replication stress responses^[1][2]. Currently, BRPF3-directed pharmacological modulators remain limited, and research applications primarily rely on genetic perturbation approaches to dissect BRPF3-HBO1-dependent H3K14 acetylation and replication origin regulation^[1].