DeltaFosB indirectly regulates Cck promoter activity
John F Enwright1, Megan Wald, Madison Paddock
1Austin College, Department of Biology, 900 N. Grand Ave., Sherman, TX 75090, USA.
Brain Research
|March 16, 2010
Summary
Short-term DeltaFosB overexpression in mice increases CREB expression and activity, influencing gene regulation in the striatum. However, DeltaFosB also regulates genes like cholecystokinin independently of CREB, revealing complex drug-induced neuroadaptations.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Chronic drug abuse induces neuroadaptations mediated by transcription factors like DeltaFosB.
- DeltaFosB and CREB (cAMP response element-binding protein) regulate overlapping gene sets in the striatum.
- The precise relationship between short-term DeltaFosB and CREB in gene regulation remained unclear.
Purpose of the Study:
- To investigate whether short-term DeltaFosB overexpression regulates target genes via CREB.
- To examine the effect of DeltaFosB on CREB expression and activity in the striatum.
- To elucidate the mechanism of cholecystokinin (Cck) gene regulation by DeltaFosB.
Main Methods:
- Overexpression of DeltaFosB in mouse striatum for 2 and 8 weeks.
- Analysis of gene expression and CREB binding to target gene promoters.
- Investigation of Cck promoter activity and the role of the CRE site.
Main Results:
- Two weeks of DeltaFosB overexpression increased striatal CREB expression, an effect that diminished by 8 weeks.
- Increased CREB binding to specific gene promoters was observed early after DeltaFosB induction.
- DeltaFosB upregulated Cck expression and promoter activity, independent of the CREB binding site.
Conclusions:
- Short-term DeltaFosB induction enhances CREB expression and promoter binding activity.
- DeltaFosB employs mechanisms beyond CREB activation to upregulate certain genes, such as Cck.
- These findings reveal complex transcriptional regulation underlying drug-induced neuroadaptations.
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