BRPF123

BRPF123 refers to the family of bromodomain and PHD finger-containing proteins BRPF1, BRPF2, and BRPF3. These proteins function as scaffolding subunits within chromatin-modifying complexes, helping to coordinate the activity of histone-modifying enzymes with genomic targets. In vertebrates, BRPF1-3 participate in the MOZ/MORF histone acetyltransferase complexes (involving KAT6A and KAT6B), guiding acetylation of histone H3 and, to a broader extent, influencing transcriptional programs during development and differentiation.

The proteins in this family share a core domain architecture that includes a bromodomain and a PHD finger, motifs known to recognize specific histone marks. The bromodomain binds acetylated lysines on histones, while the PHD finger can recognize methylated histone residues. Through these interactions, BRPF1-3 help recruit and stabilize MOZ/MORF complexes at chromatin sites, thereby modulating the local chromatin environment and the expression of target genes.

Functionally, BRPF123 proteins act as adapters that couple chromatin recognition to enzymatic activity. By directing histone acetyltransferases to particular genomic regions, they promote histone H3 acetylation and the activation or repression of gene networks essential for development, cell fate decisions, and differentiation. Their activity influences processes such as neural development, hematopoiesis, and tissue morphogenesis in model organisms, with broader implications for epigenetic regulation in mammals.

Clinical studies have linked BRPF1 mutations to neurodevelopmental disorders and intellectual disability, while alterations in BRPF2 and BRPF3 have been investigated in cancer and other developmental diseases. Ongoing research explores how BRPF1-3 contribute to chromatin regulation and how their dysregulation may be targeted in epigenetic therapies.