Coordination of Cell Cycle Progression and Mitotic Spindle Assembly Involves Histone H3 Lysine 4 Methylation by Set1/COMPASS.

ABSTRACT: Methylation of histone H3 lysine 4 (H3K4) by Set1 complex/COMPASS is a hallmark of eukaryotic chromatin, but it remains poorly understood how this post-translational modification contributes to the regulation of biological processes like the cell cycle. Here, we report a H3K4 methylation-dependent pathway in Saccharomyces cerevisiae that governs toxicity toward benomyl, a microtubule destabilizing drug. Benomyl-sensitive growth of wild-type cells required mono- and dimethylation of H3K4 and Pho23, a PHD-containing subunit of the Rpd3L complex. ?set1 and ?pho23 deletions suppressed defects associated with ipl1-2 aurora kinase mutant, an integral component of the spindle assembly checkpoint during mitosis. Benomyl resistance of ?set1 strains was accompanied by deregulation of all four tubulin genes and the phenotype was suppressed by tub2-423 and ?tub3 mutations, establishing a genetic link between H3K4 methylation and microtubule function. Most interestingly, sine wave fitting and clustering of transcript abundance time series in synchronized cells revealed a requirement for Set1 for proper cell-cycle-dependent gene expression and ?set1 cells displayed delayed entry into S phase. Disruption of G1/S regulation in ?mbp1 and ?swi4 transcription factor mutants duplicated both benomyl resistance and suppression of ipl1-2 as was observed with ?set1 Taken together our results support a role for H3K4 methylation in the coordination of cell-cycle progression and proper assembly of the mitotic spindle during mitosis.

SUBMITTER: Beilharz TH 

PROVIDER: S-EPMC5223502 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature