SP1 regulates a human SNAP-25 gene expression.

Abstract

The synaptosomal-associated protein of 25 kDa (SNAP-25) is a pre-synaptic plasma membrane protein. SNAP-25 plays an important role in synaptic vesicle membrane docking and fusion, which is involved in the regulation of neurotransmitter release. SNAP-25 has been implicated in the pathogenesis of neuropsychiatric disorders including Schizophrenia, attention-deficit hyperactivity disorder and Alzheimer's disease. We cloned a 1584 bp segment of the 5' flanking region of the human SNAP-25 gene. A series of nested deletions of the 5' flanking region fragment were subcloned into the pGL3-basic luciferase reporter plasmid. N2A cells were transfected with the SNAP-25 promoter constructs and luciferase activity was measured as an indication of promoter activity. We identified a 188 bp fragment containing the transcription initiation site as the minimal region necessary for promoter activity. Several putative cis-acting elements including SP1, hypoxia inducible factor (HIF), cAMP-response element binding protein, T-cell factor/lymphocyte enhancer factor 1 (TCF/LEF1), AP1 and the signal transducer and activator of transcription-6 (STAT6) are found in the 5' flanking region of SNAP-25 gene. Transcriptional activation and gel shift assays showed that the human SNAP-25 gene promoter contains functional SP1 response elements. Over-expression of SP1 increased SNAP-25 gene expression and inhibition of SP1-mediated transcriptional activation reduced SNAP-25 gene expression. These results suggest that SP1 plays an important role in regulation of the human SNAP-25 gene expression.

• Authors: Fang Cai, Bin Chen, Weihui Zhou, Odysseus Zis, Shengchun Liu, Robert A Holt, William G Honer, Weihong Song
• Journal: Journal of neurochemistry (J Neurochem) Vol. 105 Issue 2 Pg. 512-23 (Apr 2008) ISSN: 1471-4159 [Electronic] England
• PMID: 18194215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• SNAP25 protein, human
• Sp1 Transcription Factor
• Synaptosomal-Associated Protein 25
• mithramycin A
• Plicamycin

Topics

• Base Sequence
• Binding Sites
• Cell Line, Transformed
• Electrophoretic Mobility Shift Assay (methods)
• Gene Expression (genetics)
• Gene Expression Regulation (drug effects, genetics, physiology)
• Humans
• Plicamycin (analogs & derivatives, pharmacology)
• Promoter Regions, Genetic (physiology)
• Regulatory Sequences, Nucleic Acid
• Sequence Deletion (physiology)
• Sp1 Transcription Factor (physiology)
• Synaptosomal-Associated Protein 25 (genetics, metabolism)
• Transcription Initiation Site (physiology)
• Transcription, Genetic
• Transfection (methods)