Brn4

Brn-4, also known as Brain-4, is a transcription factor of the POU family. In humans it is encoded by the POU3F4 gene. It belongs to the POU class III group and contains a bipartite DNA-binding domain comprising a POU-specific domain and a homeodomain, enabling binding to octamer-like DNA sequences and regulation of transcription. The Brn-4 protein functions as a transcriptional regulator during neural development and otic morphogenesis, coordinating expression of downstream targets important for cell fate and structure formation.

Brn-4 expression is detected in the developing central nervous system and in the otic placode and cochlear structures, with patterns that vary by species but support roles in brain and inner ear formation. Its activity is part of broader transcriptional networks that guide neural and sensory organ development.

Genetic disruption of POU3F4 in model systems leads to abnormal inner ear development and auditory deficits. In humans, mutations in POU3F4 cause X-linked deafness, commonly referred to as DFN3 or DFNX3. A characteristic feature of affected individuals is inner ear malformation, including incomplete partition type III, sometimes accompanied by perilymphatic fistulas.

Brn-4 is studied for its role in transcriptional regulation within neural and sensory tissues, with research focusing on its interactions with other transcription factors and cofactors involved in cochlear development and congenital hearing loss. Animal and cellular models help elucidate its contribution to inner ear morphogenesis and the pathogenesis of related disorders.