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

被引:32
作者
Clough, RL
Sud, R
Davis-Silberman, N
Hertzano, R
Avraham, KB
Holley, M
Dawson, SJ
机构
[1] UCL, Sch Med, Windeyer Inst Med Sci, Dept Immunol & Mol Pathol, London, England
[2] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel
[3] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England
关键词
inner ear; hair cells; Brn-3c; POU4F3; BDNF; gene regulation; NT-3;
D O I
10.1016/j.bbrc.2004.09.074
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:372 / 381
页数:10
相关论文
共 44 条
[11]   The role of neurotrophic factors in regulating the development of inner ear innervation [J].
Fritzsch, B ;
SilosSantiago, I ;
Bianchi, LM ;
Farinas, I .
TRENDS IN NEUROSCIENCES, 1997, 20 (04) :159-164
[12]   Activation of the iNOS gene promoter by Brn-3 POU family transcription factors is dependent upon the octamer motif in the promoter [J].
Gay, RD ;
Dawson, SJ ;
Murphy, WJ ;
Russell, SW ;
Latchman, DS .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 1998, 1443 (03) :315-322
[13]  
Gorman C., 1985, DNA Cloning, A PracticalApproach
[14]   POU domain factors of the Brn-3 class recognize functional DNA elements which are distinctive, symmetrical, and highly conserved in evolution [J].
Gruber, CA ;
Rhee, JM ;
Gleiberman, A ;
Turner, EE .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (05) :2391-2400
[15]   Transcription profiling of inner ears from Pou4f3ddl/ddl identifies Gfi1 as a target of the Pou4f3 deafness gene [J].
Hertzano, R ;
Montcouquiol, M ;
Rashi-Elkeles, S ;
Elkon, R ;
Yücel, R ;
Frankel, WN ;
Rechavi, G ;
Möröy, T ;
Friedman, TB ;
Kelley, MW ;
Avraham, KB .
HUMAN MOLECULAR GENETICS, 2004, 13 (18) :2143-2153
[16]  
Huang EJ, 2001, DEVELOPMENT, V128, P2421
[17]   How hearing happens [J].
Hudspeth, AJ .
NEURON, 1997, 19 (05) :947-950
[18]   Effects of a hair cell transcription factor, Brn-3.1, gene deletion on homozygous and heterozygous mouse cochleas in adulthood and aging [J].
Keithley, EM ;
Erkman, L ;
Bennett, T ;
Lou, L ;
Ryan, AF .
HEARING RESEARCH, 1999, 134 (1-2) :71-76
[19]  
Latchman DS, 1999, J CELL PHYSIOL, V179, P126
[20]   2 PROMOTERS DIRECT TRANSCRIPTION OF THE MOUSE NT-3 GENE [J].
LEINGARTNER, A ;
LINDHOLM, D .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1994, 6 (07) :1149-1159