The DNA target site for the Brn-3 POU family transcription factors can confer responsiveness to cyclic AMP and removal of serum in neuronal cells.
The POU factors Brn-3a and Brn-3b are closely related transcription factors which are expressed in neuronal cells. The levels of the transcripts encoding these factors are regulated in opposite directions in neuronal cells by specific cellular signalling pathways with dibutyryl cyclic AMP treatment and serum removal enhancing the level of Brn-3a and reducing the level of Brn-3b expression. This opposite expression pattern is paralleled by the ability of Brn-3a to specifically transactivate a target promoter bearing its DNA binding site whereas this promoter is repressed by Brn-3b. As predicted from these observations this target promoter is strongly activated by serum removal or addition of dibutyryl cyclic AMP. Therefore changes in Brn-3a and b expression can have a functional effect on promoter activity indicating that Brn-3a and Brn-3b can regulate gene expression via a specific binding site in response to the activation of specific cellular signalling pathways. The reasons for the differences in activity between these two related factors and their role in regulating gene activity in the nervous system are discussed.
Budhram-Mahadeo
V
V
Department of Molecular Pathology, University College London Medical School, UK.
Theil
T
T
Morris
P J
PJ
Lillycrop
K A
KA
Moroy
T
T
Latchman
D S
DS
D001483:Base Sequence; D001665:Binding Sites; D001769:Blood; D003994:Bucladesine / Q000494:pharmacology; D002461:Cell Line, Transformed; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D050818:Transcription Factor Brn-3; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015533:Transcriptional Activation; D014162:Transfection
D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D050818:Transcription Factor Brn-3; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors; D003994:Bucladesine; D004247:DNA; D000242:Cyclic AMP