Brn-3c (POU4F3) regulates BDNF and NT-3 promoter activity.
Brn-3c is a transcription factor necessary for maturation and survival of hair cells in the inner ear. Mutations in Brn-3c are associated with deafness in mice and with hearing loss in humans. Mice lacking Brn-3c also show reduced innervation and loss of sensory neurons presumed to be an indirect effect of hair cell loss potentially through lower BDNF and NT-3 expression. Using transient transfection assays we show that Brn-3c is capable of activating both BDNF and NT-3 promoters in inner ear sensory epithelial cell lines. In vitro analysis shows that Brn-3c binds to specific elements within the promoters of both genes and these elements are sufficient to confer Brn-3c regulation on a heterologous promoter. Additionally, BDNF expression is reduced in the inner ear of a Brn-3c mutant mouse during embryogenesis. Our data suggest that Brn-3c may play a role in regulating neurotrophin gene expression in the inner ear.
Molecular Audiology, Department of Immunology and Molecular Pathology, UCL Centre for Auditory Research, Windeyer Institute of Medical Sciences, University College London Medical School, The Windeyer Building, Cleveland Street, London W1T 4JF, UK.
R Lee
RL
Clough
Richa
R
Sud
Noa
N
Davis-Silberman
Ronna
R
Hertzano
Karen B
KB
Avraham
Matthew
M
Holley
Sally J
SJ
Dawson
D000818:Animals; D001665:Binding Sites; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D005786:Gene Expression Regulation; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000502:physiology; D034381:Hearing Loss / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020933:Neurotrophin 3 / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D050818:Transcription Factor Brn-3; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D004268:DNA-Binding Proteins; D020933:Neurotrophin 3; D050818:Transcription Factor Brn-3; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors