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Global control of histone modification by the anaphase-promoting complex
Vijay Ramaswamy1, Jessica S Williams, Karen M Robinson
1Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
Molecular and Cellular Biology
|December 4, 2003
Summary
The anaphase-promoting complex (APC) regulates histone modifications like H3 phosphorylation and H2B/H3/H4 deacetylation during the cell cycle. This reveals a novel role for the APC in controlling global histone acetylation and H3 phosphorylation.
Area of Science:
- Molecular Biology
- Cell Biology
- Epigenetics
Background:
- Histone acetylation and phosphorylation are dynamic modifications crucial for chromosome metabolism.
- The anaphase-promoting complex (APC) is a ubiquitin ligase regulating cell cycle events.
- The APC's role in regulating histone modifications, particularly during cell cycle exit, is not fully understood.
Purpose of the Study:
- To investigate the role of the APC in regulating global histone modifications, specifically H3 phosphorylation and histone acetylation.
- To elucidate the mechanisms by which the APC controls H3 phosphorylation and dephosphorylation.
- To understand the APC's contribution to histone deacetylation during cell cycle exit.
Main Methods:
- Analysis of APC loss-of-function mutants (apc10Δ and apc11ts) in yeast.
- Genetic and biochemical analyses to study histone modification dynamics.
- Microarray analysis to assess gene expression changes related to histone modification.
Main Results:
- The APC controls global H3 S10 phosphorylation levels in cycling yeast cells.
- The APC regulates H3 dephosphorylation and global deacetylation of H2B, H3, and H4 during cell cycle exit into G0.
- APC-dependent control of H3 phosphorylation involves regulating an Aurora H3 kinase (Ipl1p) and an H3 phosphatase (GLC7).
Conclusions:
- Core histone acetylation and H3 phosphorylation are physiologically regulated by the APC.
- The APC plays a critical role in coordinating global histone modification states during cell cycle progression and exit.
- A model is proposed where APC-dependent control of both H3 kinase and phosphatase activities orchestrates global H3 phosphorylation reconfiguration.