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Volume 17, Number 20, Issue of October 15, 1997 pp. 7583-7593
Copyright ©1997 Society for Neuroscience

Identification of a Novel Repressive Element That Contributes to Neuron-Specific Gene Expression

Received May 5, 1997; revised July 21, 1997; accepted July 24, 1997.

Joseph R. M. Weber and J. H. Pate Skene

Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710

Multiple signaling pathways are thought to control the selective expression of genes over the course of neuronal differentiation. One approach to elucidating these pathways is to identify specific cis-acting elements that serve as the final targets for these signaling pathways in neural-specific genes. We now identify a novel repressive element from the growth-associated protein 43 (GAP-43) gene that can contribute to neuron-specific gene expression by inhibiting transcription in a wide range of non-neuronal cell types. This repressive element is located downstream of the GAP-43 TATA box and is highly position-dependent. When transferred to viral promoters this element preferentially inhibits 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 designate the SNOG element, because it occurs downstream of the TATA boxes of the synaptosomal-associated protein of 25 kDa and neuronal nitric oxide synthase genes, as well as the GAP-43 gene. The GAP-43 repressive element is distinct in sequence and position dependence from the repressor element 1/neuron-restrictive silencer element previously described in other neural genes and therefore is a likely target for a distinct set of signaling pathways involved in the control of neuronal differentiation.

Key words: GAP-43; gene; transcription; neuron; repressive element; SNOG element; TATA box

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