Coordination of cell cycle progression and mitotic spindle assembly involves histone H3 lysine 4 methylation by set1/COMPASS
Beilharz, Traude H.; Harrison, Paul F.; Miles, Douglas Maya; See, Michael Ming; Le, Uyen Minh Merry; Kalanon, Ming; Curtis, Melissa Jane; Hasan, Qambar; Saksouk, Julie; Margaritis, Thanasis; Holstege, Frank; Geli, Vincent; Dichtl, Bernhard
(2017) Genetics, volume 205, issue 1, pp. 185 - 199
(Article)
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
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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. Δset1 and Δpho23 deletions suppressed defects associated with ipl1-2 aurora kinase mutant, an integral component of the spindle assembly checkpoint during mitosis. Benomyl resistance of Dset1 strains was accompanied by deregulation of all four tubulin genes and the phenotype was suppressed by tub2-423 and Δtub3 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 Δset1 cells displayed delayed entry into S phase. Disruption of G1/S regulation in Δmbp1 and Δswi4 transcription factor mutants duplicated both benomyl resistance and suppression of ipl1-2 as was observed with Δset1. 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.
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Keywords: Aurora kinase, Benomyl, Cell cycle, Gene expression, Histone methylation, Genetics, Journal Article
ISSN: 0016-6731
Publisher: Genetics Society of America
Note: Funding Information: We are particularly grateful to Phillipe Pasero (Institute of Human Genetics, Montpellier, France) and Etienne Schwob (Institute of Molecular Genetics, Montpellier, France) for their help with EdU experiments and FACS analysis. We thank Sharon Dent (M. D. Anderson Cancer Center, Houston) for the ipl1-2 strain and Tim Huffaker (Cornell University, Ithaca, New York) for the tub2-423 mutant. We thank David Powell from the Monash Bioinformatics and Monash Next Generation Sequencing platforms, Micromon, and the Monash Health Translation Precinct?s Medical Genomics Facility. Publisher Copyright: © 2017 by the Genetics Society of America.
(Peer reviewed)