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

doi:10.1016/j.bbrc.2004.09.074

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

Human Molecular Genetics Biochemistry

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	372-381
Number of pages	10
Journal	Biochemical and Biophysical Research Communications
Volume	324
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2004.09.074
State	Published - 5 Nov 2004

Keywords

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

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10.1016/j.bbrc.2004.09.074

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title = "Brn-3c (POU4F3) regulates BDNF and NT-3 promoter activity",

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.",

keywords = "BDNF, Brn-3c, Gene regulation, Hair cells, Inner ear, NT-3, POU4F3",

author = "Clough, {R. Lee} and Richa Sud and Noa Davis-Silberman and Ronna Hertzano and Avraham, {Karen B.} and Matthew Holley and Dawson, {Sally J.}",

note = "Funding Information: We thank Prof. D.S. Latchman, Dr. T. Timmusk, Dr. T. Friedman, and Dr. M. Kelley for supply of materials and Dr. W. Frankel for ddl mice. This work was supported by grants from: the Wellcome Trust (064599), UCL Clinical Research & Development Committee & Friends of UCL (all to S.J.D.); and NIH Grant R01 DC005641, the Israel Science Foundation Grant No. 740/01 (K.B.A.). We thank Oracle U.K. for supply of computer equipment.",

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doi = "10.1016/j.bbrc.2004.09.074",

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AU - Clough, R. Lee

AU - Sud, Richa

AU - Davis-Silberman, Noa

AU - Hertzano, Ronna

AU - Avraham, Karen B.

AU - Holley, Matthew

AU - Dawson, Sally J.

N1 - Funding Information: We thank Prof. D.S. Latchman, Dr. T. Timmusk, Dr. T. Friedman, and Dr. M. Kelley for supply of materials and Dr. W. Frankel for ddl mice. This work was supported by grants from: the Wellcome Trust (064599), UCL Clinical Research & Development Committee & Friends of UCL (all to S.J.D.); and NIH Grant R01 DC005641, the Israel Science Foundation Grant No. 740/01 (K.B.A.). We thank Oracle U.K. for supply of computer equipment.

PY - 2004/11/5

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N2 - 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.

AB - 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.

KW - BDNF

KW - Brn-3c

KW - Gene regulation

KW - Hair cells

KW - Inner ear

KW - NT-3

KW - POU4F3

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

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