scholarly journals Steady-state and dynamic gene expression programs inSaccharomyces cerevisiaein response to variation in environmental nitrogen

2016 ◽  
Vol 27 (8) ◽  
pp. 1383-1396 ◽  
Author(s):  
Edoardo M. Airoldi ◽  
Darach Miller ◽  
Rodoniki Athanasiadou ◽  
Nathan Brandt ◽  
Farah Abdul-Rahman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Steady State ◽  
Cell Growth ◽  
Nitrogen Source ◽  
Transcriptional Control ◽  
Molecular Form ◽  
Protein Translation ◽  
Cell Growth Rate ◽  
Regulated Gene Expression

Cell growth rate is regulated in response to the abundance and molecular form of essential nutrients. In Saccharomyces cerevisiae (budding yeast), the molecular form of environmental nitrogen is a major determinant of cell growth rate, supporting growth rates that vary at least threefold. Transcriptional control of nitrogen use is mediated in large part by nitrogen catabolite repression (NCR), which results in the repression of specific transcripts in the presence of a preferred nitrogen source that supports a fast growth rate, such as glutamine, that are otherwise expressed in the presence of a nonpreferred nitrogen source, such as proline, which supports a slower growth rate. Differential expression of the NCR regulon and additional nitrogen-responsive genes results in >500 transcripts that are differentially expressed in cells growing in the presence of different nitrogen sources in batch cultures. Here we find that in growth rate–controlled cultures using nitrogen-limited chemostats, gene expression programs are strikingly similar regardless of nitrogen source. NCR expression is derepressed in all nitrogen-limiting chemostat conditions regardless of nitrogen source, and in these conditions, only 34 transcripts exhibit nitrogen source–specific differential gene expression. Addition of either the preferred nitrogen source, glutamine, or the nonpreferred nitrogen source, proline, to cells growing in nitrogen-limited chemostats results in rapid, dose-dependent repression of the NCR regulon. Using a novel means of computational normalization to compare global gene expression programs in steady-state and dynamic conditions, we find evidence that the addition of nitrogen to nitrogen-limited cells results in the transient overproduction of transcripts required for protein translation. Simultaneously, we find that that accelerated mRNA degradation underlies the rapid clearing of a subset of transcripts, which is most pronounced for the highly expressed NCR-regulated permease genes GAP1, MEP2, DAL5, PUT4, and DIP5. Our results reveal novel aspects of nitrogen-regulated gene expression and highlight the need for a quantitative approach to study how the cell coordinates protein translation and nitrogen assimilation to optimize cell growth in different environments.

scholarly journals Principles of cellular resource allocation revealed by condition-dependent proteome profiling

2017 ◽  
Author(s):  
Eyal Metzl-Raz ◽  
Moshe Kafri ◽  
Gilad Yaakov ◽  
Ilya Soifer ◽  
Yonat Gurvich ◽  
...  
Keyword(s):  
Growth Rate ◽  
Resource Allocation ◽  
Steady State ◽  
Cell Growth ◽  
Ribosomal Proteins ◽  
Budding Yeast ◽  
Protein Translation ◽  
Metabolic Rates ◽  
Proteome Profiling ◽  
State Growth

Growing cells coordinate protein translation with metabolic rates. Central to this coordination is ribosome production. Ribosomes drive cell growth, but translation of ribosomal proteins competes with production of other proteins. Theory shows that cell growth is maximized when all expressed ribosomes are constantly translating. To examine whether budding yeast function at this limit of full ribosomal usage, we profiled the proteomes of cells growing in different environments. We find that cells produce an excess of ribosomal proteins, amounting to a constant ≈8% of the proteome. Accordingly, ≈25% of ribosomal proteins expressed in rapidly growing cells do not contribute to translation. This fraction increases as growth rate decreases. These excess ribosomal proteins are employed during nutrient upshift or when forcing unneeded expression. We suggest that steadily growing cells prepare for conditions that demand increased translation by producing excess ribosomes, at the expense of lower steady-state growth rate.

NM23 gene expression correlates with cell growth rate and S-phase

1995 ◽  
Vol 60 (6) ◽  
pp. 837-842 ◽  
Author(s):  
Maria A. Caligo ◽  
Giovanna Cipollini ◽  
Lisa Fiore ◽  
Simonetta Calvo ◽  
Fulvio Basolo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Cell Growth ◽  
S Phase ◽  
Cell Growth Rate ◽  
Nm23 Gene

scholarly journals Quantifying absolute gene expression profiles reveals distinct regulation of central carbon metabolism genes in yeast

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Rosemary Yu ◽  
Egor Vorontsov ◽  
Carina Sihlbom ◽  
Jens Nielsen
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Cell Growth ◽  
Nitrogen Metabolism ◽  
Carbon Metabolism ◽  
Expression Profiles ◽  
Central Carbon Metabolism ◽  
Cell Growth Rate ◽  
Control Of Gene Expression ◽  
Central Carbon

In addition to controlled expression of genes by specific regulatory circuits, the abundance of proteins and transcripts can also be influenced by physiological states of the cell such as growth rate and metabolism. Here we examine the control of gene expression by growth rate and metabolism, by analyzing a multi-omics dataset consisting of absolute-quantitative abundances of the transcriptome, proteome, and amino acids in 22 steady-state yeast cultures. We find that transcription and translation are coordinately controlled by the cell growth rate via RNA polymerase II and ribosome abundance, but they are independently controlled by nitrogen metabolism via amino acid and nucleotide availabilities. Genes in central carbon metabolism, however, are distinctly regulated and do not respond to the cell growth rate or nitrogen metabolism as all other genes. Understanding these effects allows the confounding factors of growth rate and metabolism to be accounted for in gene expression profiling studies.

scholarly journals Principles of cellular resource allocation revealed by condition-dependent proteome profiling

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Eyal Metzl-Raz ◽  
Moshe Kafri ◽  
Gilad Yaakov ◽  
Ilya Soifer ◽  
Yonat Gurvich ◽  
...  
Keyword(s):  
Growth Rate ◽  
Resource Allocation ◽  
Steady State ◽  
Cell Growth ◽  
Ribosomal Proteins ◽  
Budding Yeast ◽  
Protein Translation ◽  
Metabolic Rates ◽  
Proteome Profiling ◽  
State Growth

Growing cells coordinate protein translation with metabolic rates. Central to this coordination is ribosome production. Ribosomes drive cell growth, but translation of ribosomal proteins competes with production of non-ribosomal proteins. Theory shows that cell growth is maximized when all expressed ribosomes are constantly translating. To examine whether budding yeast function at this limit of full ribosomal usage, we profiled the proteomes of cells growing in different environments. We find that cells produce excess ribosomal proteins, amounting to a constant ≈8% of the proteome. Accordingly, ≈25% of ribosomal proteins expressed in rapidly growing cells does not contribute to translation. Further, this fraction increases as growth rate decreases and these excess ribosomal proteins are employed when translation demands unexpectedly increase. We suggest that steadily growing cells prepare for conditions that demand increased translation by producing excess ribosomes, at the expense of lower steady-state growth rate.

scholarly journals Quantifying absolute gene expression profiles reveals distinct regulation of central carbon metabolism genes in yeast

2020 ◽  
Author(s):  
Rosemary Yu ◽  
Egor Vorontsov ◽  
Carina Sihlbom ◽  
Jens Nielsen
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Cell Growth ◽  
Carbon Metabolism ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Central Carbon Metabolism ◽  
Metabolic Parameters ◽  
Cell Growth Rate ◽  
Central Carbon

AbstractIn addition to specific regulatory circuits, gene expression is also regulated by global physiological cues such as the cell growth rate and metabolic parameters. Here we examine these global control mechanisms by analyzing an orthogonal multi-omics dataset consisting of absolute-quantitative abundances of the transcriptome, proteome, and intracellular amino acids in 22 steady-state yeast cultures. Our model indicates that transcript and protein abundance are coordinately controlled by the cell growth rate via RNA polymerase II and ribosome abundance, but are independently controlled by metabolic parameters relating to amino acid and nucleotide availability. Genes in central carbon metabolism, however, are regulated independently of these global physiological cues. Our findings can be used to augment gene expression profiling analyses in the distantly related yeast Schizosaccharomyces pombe and a human cancer cell model. Our results provide a framework to analyze gene expression profiles to gain novel biological insights, a key goal of systems biology.

Nutrient-regulated gene expression in eukaryotes

2006 ◽  
Vol 73 ◽  
pp. 85-96 ◽  
Author(s):  
Richard J. Reece ◽  
Laila Beynon ◽  
Stacey Holden ◽  
Amanda D. Hughes ◽  
Karine Rébora ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Control ◽  
Direct Interaction ◽  
Signalling Pathways ◽  
A Cell ◽  
One Step ◽  
Higher Eukaryotes ◽  
Regulated Gene Expression

The recognition of changes in environmental conditions, and the ability to adapt to these changes, is essential for the viability of cells. There are numerous well characterized systems by which the presence or absence of an individual metabolite may be recognized by a cell. However, the recognition of a metabolite is just one step in a process that often results in changes in the expression of whole sets of genes required to respond to that metabolite. In higher eukaryotes, the signalling pathway between metabolite recognition and transcriptional control can be complex. Recent evidence from the relatively simple eukaryote yeast suggests that complex signalling pathways may be circumvented through the direct interaction between individual metabolites and regulators of RNA polymerase II-mediated transcription. Biochemical and structural analyses are beginning to unravel these elegant genetic control elements.

82 Methyl Donor Supplementation Alters Cytosine Methylation and Biological Processes of Cells Cultured in Divergent Glucose Media Reflecting Improvements in Mitochondrial Respiration and Cell Growth Rate

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 109-109
Author(s):  
Matthew S Crouse ◽  
Wellison Jarles Da Silva Diniz ◽  
Joel Caton ◽  
Carl R Dahlen ◽  
Lawrence P Reynolds ◽  
...  
Keyword(s):  
Growth Rate ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Vitamin B12 ◽  
Mitochondrial Respiration ◽  
Cytosine Methylation ◽  
Biological Processes ◽  
Cell Growth Rate ◽  
Metabolic Processes ◽  
Positive Regulation

Abstract We hypothesized that supplementation of one-carbon metabolites (OCM: methionine, folate, choline, and vitamin B12) to bovine embryonic tracheal fibroblasts in divergent glucose media would alter cytosine methylation, and alterations in cytosine methylation will reflect biological processes matching previously improved mitochondrial respiration, cell proliferation, and cell growth rate data. Cells were cultured with 1g/L glucose (Low) or 4.5g/L glucose (High). Control medium (CON) contained basal concentrations of folate (0.001g/L), choline (0.001g/L), vitamin B12 (4µg/L), and methionine (0.015g/L). The OCM were supplemented at 2.5 and 5 times (2.5X and 5X, respectively) the CON media, except methionine was limited to 2X across all supplemented treatments. Cells were passaged three times in their treatment media before DNA extraction. Reduced representation bisulfite sequencing was adopted to analyze and compare the genomic methylation patterns within and across treatments using edgeR. Biological processes (BP) were retrieved based on the nearest genes of differentially methylated cytosines (P < 0.01) for each comparison between treatments. In both Low and High treatments, greater OCM increased the proportion of hypomethylated vs. hypermethylated cytosines. Functional analyses pointed out positive regulation of BP related to energy metabolism, except for the contrasts within the High group. Among the BP, we can highlight positive regulation of: GTPase activity, catalytic activity, molecular function, protein modification processes, phosphorylation, protein phosphorylation, cellular protein metabolic processes, MAPK cascade, and metabolic processes. These data support previously reported results from this experiment that showed increased mitochondrial respiration, cell proliferation, and growth rates with increasing OCM levels. We interpret these data to imply that when energy and OCM requirements are met for growth and basal methylation levels, DNA methylation levels decrease which may allow for greater transcription. Thus, OCM can be utilized for other functions such as polyamine synthesis, nucleotide synthesis, energetic metabolites, and phosphatidylcholine synthesis. USDA is an equal opportunity provider and employer.

PGE2 inhibition & interferon-gamma restoration of type 1 T cell growth rate in atopic dermatitis

1993 ◽  
Vol 6 (1) ◽  
pp. 27
Author(s):  
Sai C. Chan ◽  
Shi-Hua Li ◽  
William R. Henderson ◽  
Jon M. Hanifin
Keyword(s):  
Growth Rate ◽  
Atopic Dermatitis ◽  
T Cell ◽  
Cell Growth ◽  
Interferon Gamma ◽  
Cell Growth Rate ◽  
T Cell Growth
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