title: Differential regulation of genes encoding synaptic proteins by members of the Brn-3 subfamily of POU transcription factors.
abstract: The three members of the Brn-3 subfamily of POU transcription factors have distinct effects on target gene expression. We show that the promoter 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 target 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 SNAP-25 gene, the gene encoding the synaptic vesicle protein synapsin 1 is activated by all the Brn-3 factors, the first gene for which this activation pattern has been reported Interestingly, however, similar activation by all three Brn-3 factors can be observed if the SNAP-25 promoter 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 -283 to -126 can render a heterologous promoter responsive to activation by all three Brn-3 factors. Differences in promoter structure may thus result in differences in the response to different Brn-3 factors, thus allowing these factors to produce diverse activation patterns of neuronally expressed genes, such as those encoding different synaptic proteins.
authors.affiliation: Department of Molecular Pathology, University College London Medical School, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Morris
authors.forename: N D
authors.initials: ND
authors.lastname: Lakin
authors.forename: S J
authors.initials: SJ
authors.lastname: Dawson
authors.forename: A E
authors.initials: AE
authors.lastname: Ryabinin
authors.forename: M W
authors.initials: MW
authors.lastname: Kilimann
authors.forename: M C
authors.initials: MC
authors.lastname: Wilson
authors.forename: D S
authors.initials: DS
authors.lastname: Latchman
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017729:Presynaptic Terminals / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25; D050818:Transcription Factor Brn-3; D050820:Transcription Factor Brn-3B; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050825:Synaptosomal-Associated Protein 25; D050818:Transcription Factor Brn-3; D050820:Transcription Factor Brn-3B; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors