How Reducing Histones Affects Gene Expression
Author Information
Author(s): Barbara Celona, Assaf Weiner, Francesca Di Felice, Francesco M. Mancuso, Elisa Cesarini, Riccardo L. Rossi, Lorna Gregory, Dilair Baban, Grazisa Rossetti, Paolo Grianti, Massimiliano Pagani, Tiziana Bonaldi, Jiannis Ragoussis, Nir Friedman, Giorgio Camilloni, Marco E. Bianchi, Alessandra Agresti
Primary Institution: San Raffaele University, Milan, Italy
Hypothesis
Does a reduction in histone levels affect nucleosome occupancy and gene expression in mammalian and yeast cells?
Conclusion
Reducing histone levels leads to fewer nucleosomes, increased DNA damage sensitivity, and altered gene expression.
Supporting Evidence
- Cells lacking HMGB1 have a 20%-30% reduction in histone content.
- Nucleosome limitation increases DNA damage sensitivity.
- Global transcription increases in cells with fewer nucleosomes.
- Specific gene expression changes occur in response to histone reduction.
- Nucleosome occupancy is not uniformly affected; some sites retain higher occupancy.
- Histone reduction correlates with increased RNA transcript levels.
- Yeast nhp6 mutants show similar phenotypes to mammalian cells lacking HMGB1.
- Modeling suggests that nucleosome occupancy is influenced by histone availability.
Takeaway
When cells have fewer histones, they have fewer nucleosomes, which makes it easier for DNA to get damaged and changes how genes are expressed.
Methodology
The study involved experiments on mammalian cells and yeast, measuring histone content, nucleosome occupancy, and gene expression changes.
Limitations
The study primarily focuses on specific proteins and may not generalize to all cell types or conditions.
Statistical Information
P-Value
p<10−4
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website