IDENTIFICATION OF A NOVEL REPRESSIVE ELEMENT THAT CONTRIBUTES TO NEURON-SPECIFIC GENE-EXPRESSION

Multiple signaling pathways are thought to control the selective expre ssion of genes over the course of neuronal differentiation. One approa ch to elucidating these pathways is to identify specific cis-acting el ements that serve as the final targets for these signaling pathways in neural-specific genes. We now identify a novel repressive element fro m the growth-associated protein 43 (GAP-43) gene that can contribute t o neuron-specific gene expression by inhibiting transcription in a wid e range of non-neuronal cell types. This repressive element is located downstream of the GAP-43 TATA box and is highly position-dependent. W hen transferred to viral promoters this element preferentially inhibit s transcription in non-neuronal cells. Electrophoretic mobility shift assays show that the repressive element comprises at least two protein recognition sites. One of these is a novel sequence motif that we des ignate the SNOG element, because it occurs downstream of the TATA boxe s of the synaptosomal-associated protein of 25 kDa and neuronal nitric oxide synthase genes, as well as the GAP-43 gene. The GAP-43 repressi ve element is distinct in sequence and position dependence from the re pressor element 1/neuron-restrictive silencer element previously descr ibed in other neural genes and therefore is a likely target for a dist inct set of signaling pathways involved in the control of neuronal dif ferentiation.