Identification of a functional silencer element involved in neuron-specific expression of the synapsin I gene.
We have identified a functional silencer element (positions -231 to -211) in the human synapsin I gene that selectively represses its transcription in nonneuronal cells. Transfection experiments using synapsin I-luciferase constructs show that site-specific mutations or deletion of this silencer sequence results in expression of the reporter gene in nonneuronal cells. Moreover, the silencer element is capable of conferring repression on a heterologous promoter in nonneuronal cells. Gel-shift assays reveal the presence of a sequence-specific synapsin I silencer-binding protein in nonneuronal cell extracts but not in neuronal cell extracts. Mutagenesis studies of the silencer sequence demonstrate that formation of the specific silencer-protein complex in vitro correlates well with repression of transcription in vivo. These data indicate that the interaction between synapsin I silencer and its binding protein is involved in tissue-specific expression of the synapsin I gene. In addition, our results suggest the existence of at least one additional cis-acting element within the promoter-proximal region (positions -233 to +20) that also contributes to the neuron-specific expression of the synapsin I gene.
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021.
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L
Li
T
T
Suzuki
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N
Mori
P
P
Greengard
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics; D001483:Base Sequence; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D016716:PC12 Cells; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D016704:Synapsins / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins; D016704:Synapsins; D008156:Luciferases; D001616:beta-Galactosidase