THE DNA TARGET SITE FOR THE BRN-3 POU FAMILY TRANSCRIPTION FACTORS CAN CONFER RESPONSIVENESS TO CYCLIC-AMP AND REMOVAL OF SERUM IN NEURONALCELLS

The POU factors Brn-3a and Brn-3b are closely related transcription fa ctors which are expressed in neuronal cells. The levels of the transcr ipts encoding these factors are regulated in opposite directions in ne uronal cells by specific cellular signalling pathways with dibutyryl c yclic AMP treatment and serum removal enhancing the level of Brn-3a an d reducing the level of Brn-3b expression. This opposite expression pa ttern is paralleled by the ability of Brn-3a to specifically transacti vate a target promoter bearing its DNA binding site whereas this promo ter 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 syst em are discussed.