How Sirt6 Affects Gene Expression in Response to Stress and Aging
Author Information
Author(s): Kawahara Tiara L. A., Rapicavoli Nicole A., Wu Angela R., Qu Kun, Quake Stephen R., Chang Howard Y.
Primary Institution: Howard Hughes Medical Institute and Stanford University School of Medicine
Hypothesis
Sirt6 is a stress-responsive chromatin modifier that relocalizes to distinct target genes upon stress signaling.
Conclusion
Sirt6 dynamically relocalizes on chromatin in response to stress, influencing the expression of genes related to aging and stress response.
Supporting Evidence
- Sirt6 occupancy is highly dynamic in response to TNF-α.
- More than half of Sirt6 target genes are revealed only upon stress signaling.
- Sirt6 and RelA co-occupy a significant number of gene promoters.
- Dynamic Sirt6 localization is driven by RelA during stress response.
- Loss of Sirt6 leads to a premature aging-like phenotype in mice.
Takeaway
Sirt6 is like a helper that moves around in our cells to turn genes on and off when we're stressed or getting older.
Methodology
Genome-scale chromatin immunoprecipitation (ChIP)-chip assays were used to analyze Sirt6 binding patterns in mouse embryonic fibroblasts before and after TNF-α treatment.
Limitations
The study is based on populations of cells, which may mask individual cell behavior.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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