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- Title
SP1 regulates a human SNAP-25 gene expression.
- Authors
Fang Cai; Bin Chen; Weihui Zhou; Odysseus Zis; Shengchun Liu; Robert A. Holt; Honer, William G.; Weihong Song
- 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.
- Subjects
GENETIC transcription; GENE expression; CELL membranes; NEURAL transmission disorders; NEUROTRANSMITTERS
- Publication
Journal of Neurochemistry, 2008, Vol 105, Issue 2, p512
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2007.05167.x