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 ves icles that is expressed exclusively in neuronal cells. Here we report the isolation and characterization of the 5'-terminal region of the mu rine synapsin II gene. Primer extension and S1 nuclease protection ana lysis show that synapsin II gene transcription is initiated from a uni que site. The synapsin II gene promoter contains no canonical TATA or CAAT boxes but has putative binding sites for the transcription factor s Sp1, AP2, and NGFIA. This promoter is embedded in a large G+C-rich d omain with characteristics of a CpG island. Transfection experiments u sing synapsin II-luciferase fusion genes demonstrate that the 5'-flank ing sequence functions as a strong promoter in neuronal but not in non neuronal cells. Deletion analysis reveals the presence of a neuron-spe cific core promoter (-79 to 153) and, upstream, two positive and one n egative regulatory elements. The 5'-terminal region of the murine syna psin I gene was also cloned and sequenced. Although there is no extens ive sequence homology between the 5'-flanking regions of the synapsin I and II genes, comparison analysis has identified two regions of homo logous sequences, which may be involved in determining neuron specific ity of the core promoters of these two genes.