Clough, RL and Sud, R and Davis-Silberman, N and Hertzano, R and Avraham, KB and Holley, M and Dawson, SJ (2004) Brn-3c (POU4F3) regulates BDNF and NT-3 promoter activity. BIOCHEM BIOPH RES CO , 324 (1) 372 - 381. 10.1016/j.bbrc.2004.09.074.
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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. (C) 2004 Elsevier Inc. All rights reserved.
| Type: | Article |
|---|---|
| Title: | Brn-3c (POU4F3) regulates BDNF and NT-3 promoter activity |
| DOI: | 10.1016/j.bbrc.2004.09.074 |
| Keywords: | inner ear, hair cells, Brn-3c, POU4F3, BDNF, gene regulation, NT-3, FAMILY TRANSCRIPTION FACTORS, INNER-EAR, NEUROTROPHIC FACTOR, NERVOUS-SYSTEM, SENSORY NEURONS, DOMAIN FACTORS, CELL-LINES, GENE, EXPRESSION, MICE |
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