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

R. Lee Clough, Richa Sud, Noa Davis-Silberman, Ronna Hertzano, Karen B. Avraham, Matthew Holley, Sally J. Dawson

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)372-381
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume324
Issue number1
DOIs
StatePublished - 5 Nov 2004

Keywords

  • BDNF
  • Brn-3c
  • Gene regulation
  • Hair cells
  • Inner ear
  • NT-3
  • POU4F3

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