DIFFERENTIAL REGULATION OF GENES ENCODING SYNAPTIC PROTEINS BY MEMBERS OF THE BRN-3 SUBFAMILY OF POU TRANSCRIPTION FACTORS

The three members of the Brn-3 subfamily of POU transcription factors have distinct effects on target gene expression. We show that the prom oter of the gene encoding the presynaptic nerve terminal protein SNAP- 25 resembles previously characterised target genes in being activated by Brn-3a and Brn-3c, but being repressed by Brn-3b. Unlike other targ et genes, however, the SNAP-25 promoter can be activated by either the N- or C-terminal activation domains of Brn-3a. In contrast to the SNA P-25 gene, the gene encoding the synaptic vesicle protein synapsin I i s activated by all the Brn-3 factors, the first gene for which this ac tivation pattern has been reported. Interestingly, however, similar ac tivation by all three Brn-3 factors can be observed if the SNAP-25 pro moter is truncated by removal of sequences from -2200 to -288 relative to the transcriptional start site. Moreover, a region of the SNAP-25 promoter from -288 to -126 can render a heterologous promoter responsi ve to activation by all three Brn-3 factors. Differences in promoter s tructure may thus result in differences in the response to different B rn-3 factors, thus allowing these factors to produce diverse activatio n patterns of neuronally expressed genes, such as those encoding diffe rent synaptic proteins.