Brpf3Edit
BRPF3, or bromodomain and PHD finger containing 3, is a human protein encoded by the BRPF3 gene. It is a member of the BRPF family of chromatin regulators and serves as a key scaffolding subunit within the MOZ/MORF histone acetyltransferase complex. In this complex, BRPF3 partners with the catalytic subunits KAT6A (MOZ) and KAT6B (MORF) to regulate histone acetylation and, consequently, gene expression. The presence of a bromodomain and a PHD finger motif enables BRPF3 to recognize acetyl-lysine marks and specific histone modifications, guiding enzymatic activity to particular genomic regions and coordinating transcriptional programs across development and tissue contexts. bromodomain PHD finger histone acetyltransferase KAT6A KAT6B
Structure and domains
BRPF3 is characterized by domains that mediate its interactions with chromatin and with the MOZ/MORF complex. The bromodomain binds acetylated lysines on histone tails, providing a docking surface on chromatin, while the PHD finger engages other histone marks and influences complex recruitment. These motifs position BRPF3 as a readout module that helps target the histone acetyltransferase activity of the MOZ/MORF core to specific genomic loci. In practice, BRPF3 functions as a scaffolding component that organizes the complex and regulates the level and location of histone acetylation on substrates such as H3 and H4 tails, thereby modulating chromatin accessibility and transcription. bromodomain PHD finger histone acetylation chromatin
Biochemical function and interactions
As part of the MOZ/MORF histone acetyltransferase machinery, BRPF3 itself lacks catalytic activity but is essential for proper complex assembly and chromatin targeting. By bridging KAT6A and KAT6B with chromatin substrates, BRPF3 facilitates acetylation events that promote an open chromatin configuration and active transcription. This regulatory axis influences a broad set of gene expression programs, including those essential for cell fate decisions and developmental processes. The activity of BRPF3-containing complexes is tied to epigenetic regulation that integrates signals from developmental and environmental cues. KAT6A KAT6B MOZ MORF histone acetylation
Expression and role in development
BRPF3 is expressed across a range of tissues, with notable importance in contexts where precise epigenetic control of gene expression is required, such as during development and in the nervous system. Studies in model organisms indicate that BRPF family proteins contribute to neural development and organogenesis by shaping chromatin states and transcriptional programs. The redundancy and specialization among BRPF family members (including BRPF1 and BRPF2) underscore a coordinated role in development, with BRPF3 acting to refine acetylation-dependent regulation in a tissue- and context-specific manner. epigenetics neural development BRPF1 BRPF2
Clinical significance
Because BRPF3 is part of bromodomain-containing chromatin regulators, alterations in its expression or function can perturb histone acetylation patterns and downstream gene expression. Dysregulation of BRPF3 or its partners in the MOZ/MORF complex has potential implications for cancer biology and developmental disorders, given the importance of epigenetic control in cell proliferation, differentiation, and lineage specification. As interest in targeted epigenetic therapies grows, BRPF3 and related BRPF family members are often considered in discussions of bromodomain-targeting strategies aimed at modulating chromatin landscapes in disease. cancer epigenetic therapy KAT6A KAT6B
Evolution and orthologs
BRPF3 is part of a small, conserved family of bromodomain and PHD finger-containing regulators that spans vertebrates. Orthologs of BRPF3 can be found across mammals, birds, reptiles, amphibians, and many fish, illustrating the evolutionary importance of BRPF-mediated chromatin regulation. The overall domain architecture—bromodomain and PHD finger within a scaffolding subunit that associates with KAT6A/B—appears preserved, supporting a fundamental role in controlling histone acetylation and gene expression across species. BRPF1 BRPF2 evolution