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

Autor: Qambar Hasan, Vincent Géli, Melissa Jane Curtis, Traude H. Beilharz, Thanasis Margaritis, Michael Ming See, Paul Harrison, Bernhard Dichtl, Ming Kalanon, Julie Saksouk, Douglas Maya Miles, Uyen Minh Merry Le, Frank C. P. Holstege
Přispěvatelé: Monash University [Melbourne], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre for Cellular and Molecular Biology, School of Life and Environmental Sciences, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Princess Máxima Center for Pediatric Oncology
Rok vydání: 2016
Předmět:
Zdroj: Genetics, 205(1), 185. Genetics Society of America
Genetics
Genetics, 2017, 205 (1), pp.185-199. ⟨10.1534/genetics.116.194852⟩
Genetics, Genetics Society of America, 2017, 205 (1), pp.185-199. ⟨10.1534/genetics.116.194852⟩
ISSN: 1943-2631
0016-6731
DOI: 10.1534/genetics.116.194852⟩
Popis: 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. 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 Δset1 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.
Databáze: OpenAIRE