Coordination of Cell Cycle Progression and Mitotic Spindle Assembly Involves Histone H3 Lysine 4 Methylation by
Traude H Beilharz1, Paul F Harrison1,2, Douglas Maya Miles3
1Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria 3800, Australia.
Genetics
|January 5, 2017
Summary
Histone H3 lysine 4 (H3K4) methylation by the Set1 complex regulates cell cycle progression and response to benomyl, a microtubule drug. This epigenetic mark is crucial for coordinating cell division and spindle assembly in yeast.
Area of Science:
- Epigenetics and Molecular Biology
- Cell Biology
- Yeast Genetics
Background:
- Histone H3 lysine 4 (H3K4) methylation is a key epigenetic mark in eukaryotes.
- Its role in regulating biological processes, particularly the cell cycle, is not fully understood.
- Understanding H3K4 methylation's function is critical for deciphering gene regulation.
Purpose of the Study:
- To investigate the role of H3K4 methylation in Saccharomyces cerevisiae.
- To elucidate the pathway linking H3K4 methylation to benomyl toxicity and cell cycle control.
- To establish the genetic connections between H3K4 methylation, microtubule function, and cell division.
Main Methods:
- Genetic analysis of yeast mutants (Δset1, Δpho23, ipl1-2, tub2-423, Δtub3, Δmbp1, Δswi4).
- Phenotypic analysis of benomyl sensitivity and cell cycle progression.
- Transcriptome analysis using sine wave fitting and clustering of time-series data.
Main Results:
- H3K4 mono- and dimethylation and Pho23 are required for benomyl sensitivity.
- Set1 and Pho23 deletions suppressed defects in the aurora kinase ipl1-2 mutant.
- Δset1 strains showed benomyl resistance, tubulin gene deregulation, and delayed S phase entry.
- Disrupting G1/S regulators mimicked Δset1 phenotypes.
Conclusions:
- H3K4 methylation is essential for coordinating cell cycle progression in response to environmental stress.
- The Set1 complex plays a critical role in regulating gene expression during the cell cycle.
- H3K4 methylation is linked to microtubule function and proper mitotic spindle assembly.
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