scholarly journals INO80 Chromatin Remodelling Coordinates Metabolic Homeostasis with Cell Division

2017 ◽  
Author(s):  
Graeme J. Gowans ◽  
Alicia N. Schep ◽  
Ka Man Wong ◽  
Devin A. King ◽  
William J. Greenleaf ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Division ◽  
Chromatin Accessibility ◽  
Chromatin Remodelling ◽  
Chromatin Remodelling Complex ◽  
Periodic Gene ◽  
Yeast Metabolic Cycle ◽  
Mutant Cells ◽  
Metabolic Cycle ◽  
Periodic Gene Expression

ABSTRACTAdaptive survival requires the coordination of nutrient availability with expenditure of cellular resources. For example, in nutrient-limited environments, 50% of all S. cerevisiae genes synchronize and exhibit periodic bursts of expression in coordination with respiration and cell division in the Yeast Metabolic Cycle (YMC). Despite the importance of metabolic and proliferative synchrony, the majority of YMC regulators are currently unknown. Here we demonstrate that the INO80 chromatin-remodelling complex is required to coordinate respiration and cell division with periodic gene expression. Specifically, INO80 mutants have severe defects in oxygen consumption and promiscuous cell division that is no longer coupled with metabolic status. In mutant cells, chromatin accessibility of periodic genes, including TORC-responsive genes, is relatively static, concomitant with severely attenuated gene expression. Collectively, these results reveal that the INO80 complex mediates metabolic signaling to chromatin in order to restrict proliferation to metabolically optimal states.

scholarly journals Oscillatory Phosphorylation of Yeast Fus3 MAP Kinase Controls Periodic Gene Expression and Morphogenesis

2008 ◽  
Vol 18 (23) ◽  
pp. 1897
Author(s):  
Zoe Hilioti ◽  
Walid Sabbagh ◽  
Saurabh Paliwal ◽  
Adriel Bergmann ◽  
Marcus D. Goncalves ◽  
...  
Keyword(s):  
Gene Expression ◽  
Map Kinase ◽  
Periodic Gene ◽  
Periodic Gene Expression

scholarly journals Extensive Regulation of Metabolism and Growth during the Cell Division Cycle

2014 ◽  
Author(s):  
Nikolai Slavov ◽  
David Botstein ◽  
Amy Caudy
Keyword(s):  
Gene Expression ◽  
Oxygen Consumption ◽  
Cell Division ◽  
Single Cell ◽  
Single Cells ◽  
Emergent Behavior ◽  
Yeast Cells ◽  
Physiological Data ◽  
Synchronized Cultures ◽  
Metabolic Cycle

Yeast cells grown in culture can spontaneously synchronize their respiration, metabolism, gene expression and cell division. Such metabolic oscillations in synchronized cultures reflect single-cell oscillations, but the relationship between the oscillations in single cells and synchronized cultures is poorly understood. To understand this relationship and the coordination between metabolism and cell division, we collected and analyzed DNA-content, gene-expression and physiological data, at hundreds of time-points, from cultures metabolically-synchronized at different growth rates, carbon sources and biomass densities. The data enabled us to extend and generalize our mechanistic model, based on ensemble average over phases (EAP), connecting the population-average gene-expression of asynchronous cultures to the gene-expression dynamics in the single-cells comprising the cultures. The extended model explains the carbon-source specific growth-rate responses of hundreds of genes. Our physiological data demonstrate that the frequency of metabolic cycling in synchronized cultures increases with the biomass density, suggesting that this cycling is an emergent behavior, resulting from the entraining of the single-cell metabolic cycle by a quorum-sensing mechanism, and thus underscoring the difference between metabolic cycling in single cells and in synchronized cultures. Measurements of constant levels of residual glucose across metabolically synchronized cultures indicate that storage carbohydrates are required to fuel not only the G1/S transition of the division cycle but also the metabolic cycle. Despite the large variation in profiled conditions and in the scale of their dynamics, most genes preserve invariant dynamics of coordination with each other and with the rate of oxygen consumption. Similarly, the G1/S transition always occurs at the beginning, middle or end of the high oxygen consumption phases, analogous to observations in human and drosophila cells. These results highlight evolutionary conserved coordination among metabolism, cell growth and division.

scholarly journals Cell cycle Start is coupled to entry into the yeast metabolic cycle across diverse strains and growth rates

2016 ◽  
Vol 27 (1) ◽  
pp. 64-74 ◽  
Author(s):  
Anthony J. Burnetti ◽  
Mert Aydin ◽  
Nicolas E. Buchler
Keyword(s):  
Cell Cycle ◽  
Oxygen Consumption ◽  
Cell Division ◽  
Dna Replication ◽  
Growth Rates ◽  
Quantitative Relationship ◽  
High Temporal Resolution ◽  
Different Strains ◽  
Yeast Metabolic Cycle ◽  
Metabolic Cycle

Cells have evolved oscillators with different frequencies to coordinate periodic processes. Here we studied the interaction of two oscillators, the cell division cycle (CDC) and the yeast metabolic cycle (YMC), in budding yeast. Previous work suggested that the CDC and YMC interact to separate high oxygen consumption (HOC) from DNA replication to prevent genetic damage. To test this hypothesis, we grew diverse strains in chemostat and measured DNA replication and oxygen consumption with high temporal resolution at different growth rates. Our data showed that HOC is not strictly separated from DNA replication; rather, cell cycle Start is coupled with the initiation of HOC and catabolism of storage carbohydrates. The logic of this YMC–CDC coupling may be to ensure that DNA replication and cell division occur only when sufficient cellular energy reserves have accumulated. Our results also uncovered a quantitative relationship between CDC period and YMC period across different strains. More generally, our approach shows how studies in genetically diverse strains efficiently identify robust phenotypes and steer the experimentalist away from strain-specific idiosyncrasies.

scholarly journals Live-cell monitoring of periodic gene expression in synchronous human cells identifies Forkhead genes involved in cell cycle control

2012 ◽  
Vol 23 (16) ◽  
pp. 3079-3093 ◽  
Author(s):  
Gavin D. Grant ◽  
Joshua Gamsby ◽  
Viktor Martyanov ◽  
Lionel Brooks ◽  
Lacy K. George ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Dna Binding ◽  
Luciferase Activity ◽  
Binding Motif ◽  
Sequencing Analysis ◽  
Peak Expression ◽  
Periodic Gene ◽  
Regulated Gene Expression ◽  
Periodic Gene Expression

We developed a system to monitor periodic luciferase activity from cell cycle–regulated promoters in synchronous cells. Reporters were driven by a minimal human E2F1 promoter with peak expression in G1/S or a basal promoter with six Forkhead DNA-binding sites with peak expression at G2/M. After cell cycle synchronization, luciferase activity was measured in live cells at 10-min intervals across three to four synchronous cell cycles, allowing unprecedented resolution of cell cycle–regulated gene expression. We used this assay to screen Forkhead transcription factors for control of periodic gene expression. We confirmed a role for FOXM1 and identified two novel cell cycle regulators, FOXJ3 and FOXK1. Knockdown of FOXJ3 and FOXK1 eliminated cell cycle–dependent oscillations and resulted in decreased cell proliferation rates. Analysis of genes regulated by FOXJ3 and FOXK1 showed that FOXJ3 may regulate a network of zinc finger proteins and that FOXK1 binds to the promoter and regulates DHFR, TYMS, GSDMD, and the E2F binding partner TFDP1. Chromatin immunoprecipitation followed by high-throughput sequencing analysis identified 4329 genomic loci bound by FOXK1, 83% of which contained a FOXK1-binding motif. We verified that a subset of these loci are activated by wild-type FOXK1 but not by a FOXK1 (H355A) DNA-binding mutant.

scholarly journals Coupling among growth rate response, metabolic cycle, and cell division cycle in yeast

2011 ◽  
Vol 22 (12) ◽  
pp. 1997-2009 ◽  
Author(s):  
Nikolai Slavov ◽  
David Botstein
Keyword(s):  
Growth Rate ◽  
Oxygen Consumption ◽  
Cell Division ◽  
Carbon Source ◽  
Oxidative Metabolism ◽  
Sole Source ◽  
Cell Division Cycle ◽  
Steady State Responses ◽  
Yeast Metabolic Cycle ◽  
Metabolic Cycle

We studied the steady-state responses to changes in growth rate of yeast when ethanol is the sole source of carbon and energy. Analysis of these data, together with data from studies where glucose was the carbon source, allowed us to distinguish a “universal” growth rate response (GRR) common to all media studied from a GRR specific to the carbon source. Genes with positive universal GRR include ribosomal, translation, and mitochondrial genes, and those with negative GRR include autophagy, vacuolar, and stress response genes. The carbon source–specific GRR genes control mitochondrial function, peroxisomes, and synthesis of vitamins and cofactors, suggesting this response may reflect the intensity of oxidative metabolism. All genes with universal GRR, which comprise 25% of the genome, are expressed periodically in the yeast metabolic cycle (YMC). We propose that the universal GRR may be accounted for by changes in the relative durations of the YMC phases. This idea is supported by oxygen consumption data from metabolically synchronized cultures with doubling times ranging from 5 to 14 h. We found that the high oxygen consumption phase of the YMC can coincide exactly with the S phase of the cell division cycle, suggesting that oxidative metabolism and DNA replication are not incompatible.

scholarly journals A conserved cell growth cycle can account for the environmental stress responses of divergent eukaryotes

2012 ◽  
Vol 23 (10) ◽  
pp. 1986-1997 ◽  
Author(s):  
Nikolai Slavov ◽  
Edoardo M. Airoldi ◽  
Alexander van Oudenaarden ◽  
David Botstein
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Oxygen Consumption ◽  
Heat Stress ◽  
Cell Division ◽  
Environmental Stress ◽  
Fission Yeast ◽  
Budding Yeast ◽  
Cell Division Cycle ◽  
Metabolic Cycle

The respiratory metabolic cycle in budding yeast (Saccharomyces cerevisiae) consists of two phases that are most simply defined phenomenologically: low oxygen consumption (LOC) and high oxygen consumption (HOC). Each phase is associated with the periodic expression of thousands of genes, producing oscillating patterns of gene expression found in synchronized cultures and in single cells of slowly growing unsynchronized cultures. Systematic variation in the durations of the HOC and LOC phases can account quantitatively for well-studied transcriptional responses to growth rate differences. Here we show that a similar mechanism—transitions from the HOC phase to the LOC phase—can account for much of the common environmental stress response (ESR) and for the cross-protection by a preliminary heat stress (or slow growth rate) to subsequent lethal heat stress. Similar to the budding yeast metabolic cycle, we suggest that a metabolic cycle, coupled in a similar way to the ESR, in the distantly related fission yeast, Schizosaccharomyces pombe, and in humans can explain gene expression and respiratory patterns observed in these eukaryotes. Although metabolic cycling is associated with the G0/G1 phase of the cell division cycle of slowly growing budding yeast, transcriptional cycling was detected in the G2 phase of the division cycle in fission yeast, consistent with the idea that respiratory metabolic cycling occurs during the phases of the cell division cycle associated with mass accumulation in these divergent eukaryotes.

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