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Regional differences in gene expression and promoter usage in aged human brains
Luba M Pardo1, Patrizia Rizzu, Margherita Francescatto
1Section Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
Neurobiology of Aging
|February 23, 2013
Summary
Alternative promoter usage drives gene expression differences in aged human brain regions like the hippocampus and striatum, impacting neurodevelopmental genes and signaling pathways.
Area of Science:
- Neuroscience
- Genomics
- Epigenetics
Background:
- Gene expression patterns change with age in the human brain.
- Understanding regional differences in gene expression is crucial for aging research.
Purpose of the Study:
- To characterize the promoterome across five distinct aged human brain regions.
- To investigate the role of alternative promoter usage and DNA methylation in regional gene expression differences.
Main Methods:
- High-throughput cap analysis of gene expression (CAGE) was employed.
- Over 71 million CAGE tags were sequenced, covering 70,202 promoter regions and 16,888 genes.
- DNA methylation analysis was performed to assess its influence on gene expression.
Main Results:
- Over 7,000 transcripts showed differential expression, primarily due to alternative promoter usage.
- A significant portion (7%) of differentially expressed genes were identified as neurodevelopmental transcription factors.
- Fibroblast growth factor and wnt signaling pathways were overrepresented in the hippocampus and striatum.
- DNA methylation had a limited impact on the observed expression profiles, despite mapping within genes.
Conclusions:
- Alternative promoter usage is a key mechanism underlying regional gene expression variability in the aged human brain.
- The findings highlight the importance of promoter-level regulation in brain aging.
- The study identifies specific signaling pathways and neurodevelopmental genes involved in regional brain differences in old age.
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