title: Identification of a novel repressive element that contributes to neuron-specific gene expression.
abstract: 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.
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Weber
authors.forename: J H
authors.initials: JH
authors.lastname: Skene
mesh_terms: D000818:Animals; D001483:Base Sequence; D019922:GAP-43 Protein; D005786:Gene Expression Regulation; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050825:Synaptosomal-Associated Protein 25; D016385:TATA Box / Q000235:genetics
chemical_list: D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D019001:Nitric Oxide Synthase