NEURON-SPECIFIC EXPRESSION OF THE SYNAPSIN-II GENE IS DIRECTED BY A SPECIFIC CORE PROMOTER AND UPSTREAM REGULATORY ELEMENTS

Synapsin II is an abundant peripheral membrane protein of synaptic vesicles that is expressed exclusively in neuronal cells. Here we report the isolation and characterization of the 5'-terminal region of the murine synapsin II gene. Primer extension and S1 nuclease protection analysis show that synapsin II gene transcription is initiated from a unique site. The synapsin II gene promoter contains no canonical TATA or CAAT boxes but has putative binding sites for the transcription factors Sp1, AP2, and NGFIA. This promoter is embedded in a large G+C-rich domain with characteristics of a CpG island. Transfection experiments using synapsin II-luciferase fusion genes demonstrate that the 5'-flanking sequence functions as a strong promoter in neuronal but not in nonneuronal cells. Deletion analysis reveals the presence of a neuron-specific core promoter (-79 to 153) and, upstream, two positive and one negative regulatory elements. The 5'-terminal region of the murine synapsin I gene was also cloned and sequenced. Although there is no extensive sequence homology between the 5'-flanking regions of the synapsin I and II genes, comparison analysis has identified two regions of homologous sequences, which may be involved in determining neuron specificity of the core promoters of these two genes.