Brn-3c (POU4F3) regulates BDNF and NT-3 promoter activity

Biochem Biophys Res Commun. 2004 Nov 5;324(1):372-81. doi: 10.1016/j.bbrc.2004.09.074.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Brain-Derived Neurotrophic Factor / genetics*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Exons
  • Gene Expression Regulation*
  • Hair Cells, Auditory, Inner / cytology
  • Hair Cells, Auditory, Inner / physiology
  • Hearing Loss / genetics
  • Humans
  • Mice
  • Mice, Knockout
  • Neurotrophin 3 / genetics*
  • Neurotrophin 3 / metabolism
  • Promoter Regions, Genetic*
  • Rats
  • Transcription Factor Brn-3
  • Transcription Factor Brn-3C
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Brain-Derived Neurotrophic Factor
  • DNA-Binding Proteins
  • Neurotrophin 3
  • Transcription Factor Brn-3
  • Transcription Factor Brn-3C
  • Transcription Factors