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Heat shock, histone H3 phosphorylation and the cell cycle
Mark H Dyson1, Stuart Thomson, Louis C Mahadevan
1Nuclear Signalling Laboratory, Department of Biochemistry, University of Oxford, Oxford, UK.
Cell Cycle (Georgetown, Tex.)
|December 22, 2004
Summary
Heat shock triggers histone H3 phosphorylation changes in both fruit flies and mice, but cell cycle effects in mouse cells complicate direct comparisons of this stress response. This highlights key differences in cellular responses to heat shock.
Area of Science:
- Molecular Biology
- Cellular Stress Response
- Epigenetics
Background:
- Heat shock induces conserved stress responses across species, involving molecular participants like histone modifications.
- Histone H3 phosphorylation changes have been observed in response to heat shock in both Drosophila and mouse models.
- Previous studies identified differences in these responses between Drosophila and mouse systems.
Purpose of the Study:
- To summarize and highlight the differences in heat shock-modulated histone phosphorylation between Drosophila and mouse cells.
- To investigate the complexity of the nucleosomal response to heat shock in mouse cells throughout the cell cycle.
- To analyze how cell cycle effects in mouse cells may indirectly influence heat shock-induced changes, complicating inter-species comparisons.
Main Methods:
- Comparative analysis of genome-wide and gene-specific histone H3 phosphorylation data.
- Utilizing experimental models: Drosophila polytene chromosome puffing and cultured mouse cells with hsp70 mRNA induction.
- Monitoring nucleosomal response (histone H3 and HMGN1 phosphorylation) across the cell cycle in mouse cells.
Main Results:
- Heat shock induces distinct patterns of histone H3 phosphorylation in Drosophila and mouse cells, despite conserved stress response mechanisms.
- In mouse cells, heat shock-induced histone H3 and HMGN1 phosphorylation is influenced by the cell cycle stage.
- Cell cycle-dependent effects in mouse cells suggest some heat shock responses may be indirect consequences of cell cycle disruption.
Conclusions:
- Direct comparisons of heat shock-induced histone phosphorylation between Drosophila and mouse cells are complicated by cell cycle-dependent indirect effects in mouse cells.
- The cell cycle plays a significant role in modulating the nucleosomal response to heat shock in mammalian cells.
- Understanding these differences is crucial for accurately interpreting conserved and divergent stress response pathways.