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The human semaphorin 6B gene is down regulated by PPARs
Philippe Collet1, Lionel Domenjoud, Marie Dominique Devignes
1EA 3446 "Peroxisome Proliferators," Faculty of Sciences, BP 239, University Henri Poincaré-Nancy 1, 54506 Vandoeuvre-les-Nancy, France. philippecollet5@aol.com
Genomics
|June 5, 2004
Summary
Peroxisome proliferator-activated receptors (PPARs) regulate gene expression. Researchers identified a novel PPAR binding site regulating the human semaphorin 6B gene, demonstrating PPAR activators decrease its expression.
Area of Science:
- Molecular Biology
- Genetics
- Neuroscience
Background:
- Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors involved in gene regulation.
- PPARs form heterodimers with retinoid X receptors and bind to specific DNA sequences.
- PPARs play roles in brain development, neuronal differentiation, and CNS lipid metabolism.
Purpose of the Study:
- To develop an affinity method for isolating PPAR binding sites and identifying novel PPAR target genes.
- To investigate the regulation of the human semaphorin 6B (HSA)SEMA6B gene by PPARs.
Main Methods:
- Developed an antibody-based affinity method to isolate human genomic fragments with PPAR binding sites.
- Used gel mobility shift, supershift, and competition assays to confirm PPAR binding.
- Performed transfection experiments and gene expression analysis in glioblastoma cells.
Main Results:
- Identified a novel PPAR binding site (ISF5148) located 8.5 kb upstream of the (HSA)SEMA6B gene.
- Demonstrated that ISF5148 specifically binds to PPARs and exhibits transregulation potential.
- Showed that PPARalpha agonists (clofibrate, Wy-14,643) down-regulate (HSA)SEMA6B expression in human glioblastoma cells.
Conclusions:
- Established that PPAR activators diminish the expression of the human (HSA)SEMA6B gene.
- Highlighted the relevance of PPARs in the central nervous system and suggested cross-talk with retinoic acid pathways.