Activation of the alpha-internexin promoter by the Brn-3a transcription factor is dependent on the N-terminal region of the protein.
The Brn-3a, Brn-3b, and Brn-3c proteins are closely related POU (Pit-Oct-Unc) family transcription factors which are expressed predominantly in neuronal cells. We have identified the alpha-internexin gene as the first reported, neuronally expressed, target gene whose promoter activity is modulated by these factors. Both the Brn-3a and Brn-3c factors can activate the alpha-internexin promoter while Brn-3b represses it and can prevent activation by Brn-3a. Using chimeric constructs containing different regions of Brn-3a or Brn-3b, we show that activation of the alpha-internexin promoter requires the N-terminal region of Brn-3a. In contrast the activation by Brn-3a but not Brn-3b of an artificial promoter containing a synthetic Brn-3 binding site can be shown using the same constructs to be dependent on the POU domain of Brn-3a. Moreover, the isolated POU domain of Brn-3a can activate this artificial promoter but not the alpha-internexin promoter. Hence Brn-3a contains two distinct transactivation domains, at the N terminus and within the POU domain, whose effect is dependent upon the target promoter. The relationship of gene transactivation by Brn-3a to its ability to transform primary cells which is also dependent on the N-terminal region of the protein is discussed.
Department of Molecular Pathology, University College London Medical School, United Kingdom.
V
V
Budhram-Mahadeo
P J
PJ
Morris
N D
ND
Lakin
T
T
Theil
G Y
GY
Ching
K A
KA
Lillycrop
T
T
Möröy
R K
RK
Liem
D S
DS
Latchman
D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D007381:Intermediate Filament Proteins; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050818:Transcription Factor Brn-3; D050820:Transcription Factor Brn-3B; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors / Q000378:metabolism*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D007381:Intermediate Filament Proteins; D009838:Oligodeoxyribonucleotides; D050818:Transcription Factor Brn-3; D050820:Transcription Factor Brn-3B; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors; C046643:alpha-internexin; D003994:Bucladesine