scholarly journals SIR2 Expression Noise Can Generate Heterogeneity in Viability but Does Not Affect Cell-to-Cell Epigenetic Silencing of Subtelomeric URA3 in Yeast

2020 ◽  
Vol 10 (9) ◽  
pp. 3435-3443
Author(s):  
Jian Liu ◽  
Laureline Mosser ◽  
Catherine Botanch ◽  
Jean-Marie François ◽  
Jean-Pascal Capp
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Epigenetic Modification ◽  
Epigenetic Silencing ◽  
Cell Heterogeneity ◽  
Gene Expression Noise ◽  
Expression Noise ◽  
Cell Expression ◽  
Cell To Cell Variability ◽  
Epigenetic Processes

Abstract Chromatin structure clearly modulates gene expression noise, but the reverse influence has never been investigated, namely how the cell-to-cell expression heterogeneity of chromatin modifiers may generate variable rates of epigenetic modification. Sir2 is a well-characterized histone deacetylase of the Sirtuin family. It strongly influences chromatin silencing, especially at telomeres, subtelomeres and rDNA. This ability to influence epigenetic landscapes makes it a good model to study the largely unexplored interplay between gene expression noise and other epigenetic processes leading to phenotypic diversification. Here, we addressed this question by investigating whether noise in the expression of SIR2 was associated with cell-to-cell heterogeneity in the frequency of epigenetic silencing at subtelomeres in Saccharomyces cerevisiae. Using cell sorting to isolate subpopulations with various expression levels, we found that heterogeneity in the cellular concentration of Sir2 does not lead to heterogeneity in the epigenetic silencing of subtelomeric URA3 between these subpopulations. We also noticed that SIR2 expression noise can generate cell-to-cell variability in viability, with lower levels being associated with better viability. This work shows that SIR2 expression fluctuations are not sufficient to generate cell-to-cell heterogeneity in the epigenetic silencing of URA3 at subtelomeres in Saccharomyces cerevisiae but can strongly affect cellular viability.

Division time-based amplifiers for stochastic gene expression

2015 ◽  
Vol 11 (9) ◽  
pp. 2417-2428 ◽  
Author(s):  
Haohua Wang ◽  
Zhanjiang Yuan ◽  
Peijiang Liu ◽  
Tianshou Zhou
Keyword(s):  
Gene Expression ◽  
Cell Division ◽  
Stochastic Gene Expression ◽  
Noise Sources ◽  
Gene Expression Noise ◽  
Expression Noise ◽  
Stochastic Switching ◽  
Cell To Cell Variability ◽  
Birth Death

While cell-to-cell variability is a phenotypic consequence of gene expression noise, sources of this noise may be complex – apart from intrinsic sources such as the random birth/death of mRNA and stochastic switching between promoter states, there are also extrinsic sources of noise such as cell division where division times are either constant or random.

scholarly journals Author response: Fitness effects of altering gene expression noise in Saccharomyces cerevisiae

2018 ◽  
Author(s):  
Fabien Duveau ◽  
Andrea Hodgins-Davis ◽  
Brian PH Metzger ◽  
Bing Yang ◽  
Stephen Tryban ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Author Response ◽  
Gene Expression Noise ◽  
Fitness Effects ◽  
Expression Noise

scholarly journals Fitness effects of altering gene expression noise in Saccharomyces cerevisiae

2018 ◽  
Author(s):  
Fabien Duveau ◽  
Andrea Hodgins-Davis ◽  
Brian P.H. Metzger ◽  
Bing Yang ◽  
Stephen Tryban ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Expression Level ◽  
Gene Expression Noise ◽  
Expression Levels ◽  
Fitness Effects ◽  
Expression Noise ◽  
Average Expression Level ◽  
The Difference ◽  
The Impact

AbstractGene expression noise is an evolvable property of biological systems that describes differences in gene expression among genetically identical cells in the same environment. Prior work has shown that expression noise is heritable and can be shaped by natural selection, but the impact of variation in expression noise on organismal fitness has proven difficult to measure. Here, we quantify the fitness effects of altering expression noise for the TDH3 gene in Saccharomyces cerevisiae. We show that increases in expression noise can be deleterious or beneficial depending on the difference between the average expression level of a genotype and the expression level maximizing fitness. We also show that a simple model relating single-cell expression levels to population growth produces patterns that are consistent with our empirical data. We use this model to explore a broad range of average expression levels and expression noise, providing additional insight into the fitness effects of variation in expression noise.

scholarly journals Fitness effects of altering gene expression noise in Saccharomyces cerevisiae

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Fabien Duveau ◽  
Andrea Hodgins-Davis ◽  
Brian PH Metzger ◽  
Bing Yang ◽  
Stephen Tryban ◽  
...  
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Expression Level ◽  
Gene Expression Noise ◽  
Expression Levels ◽  
Fitness Effects ◽  
Expression Noise ◽  
Average Expression Level ◽  
The Difference ◽  
The Impact

Gene expression noise is an evolvable property of biological systems that describes differences in expression among genetically identical cells in the same environment. Prior work has shown that expression noise is heritable and can be shaped by selection, but the impact of variation in expression noise on organismal fitness has proven difficult to measure. Here, we quantify the fitness effects of altering expression noise for the TDH3 gene in Saccharomyces cerevisiae. We show that increases in expression noise can be deleterious or beneficial depending on the difference between the average expression level of a genotype and the expression level maximizing fitness. We also show that a simple model relating single-cell expression levels to population growth produces patterns consistent with our empirical data. We use this model to explore a broad range of average expression levels and expression noise, providing additional insight into the fitness effects of variation in expression noise.

scholarly journals Gene expression noise produces cell-to-cell heterogeneity in eukaryotic homologous recombination rate

2019 ◽  
Author(s):  
Jian Liu ◽  
Jean-Marie François ◽  
Jean-Pascal Capp
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Homologous Recombination ◽  
Genome Stability ◽  
Phenotypic Diversity ◽  
Cell Heterogeneity ◽  
Gene Expression Noise ◽  
Expression Noise ◽  
Expression Of Genes ◽  
Evolutionary Consequences

AbstractVariation in gene expression among genetically identical individual cells (called gene expression noise) directly contributes to phenotypic diversity. Whether such variation can impact genome stability and lead to variation in genotype remains poorly explored. We addressed this question by investigating whether noise in the expression of genes affecting homologous recombination (HR) activity either directly (RAD52) or indirectly (RAD27) confers cell-to-cell heterogeneity in HR rate inSaccharomyces cerevisiae. Using cell sorting to isolate subpopulations with various expression levels, we show that spontaneous HR rate is highly heterogeneous from cell-to-cell in clonal populations depending on the cellular amount of proteins affecting HR activity. Phleomycin-induced HR is even more heterogeneous, showing thatRAD27expression noise strongly affects the rate of recombination from cell-to-cell. Strong variations in HR rate between subpopulations are not correlated to strong changes in cell cycle stage. Moreover, this heterogeneity occurs even when simultaneously sorting cells at equal expression level of another gene involved in DNA damage response (BMH1) that is upregulated by DNA damage, showing that the initiating DNA damage is not responsible for the observed heterogeneity in HR rate. Thus gene expression noise seems mainly responsible for this phenomenon. Finally, HR rate non-linearly scales with Rad27 levels showing that total amount of HR cannot be explained solely by the time- or population-averaged Rad27 expression. Altogether, our data reveal interplay between heterogeneity at the gene expression and genetic levels in the production of phenotypic diversity with evolutionary consequences from microbial to cancer cell populations.

Reduction in gene expression noise by targeted increase in accessibility at gene loci

2021 ◽  
Vol 118 (42) ◽  
pp. e2018640118
Author(s):  
LaTasha C. R. Fraser ◽  
Ryan J. Dikdan ◽  
Supravat Dey ◽  
Abhyudai Singh ◽  
Sanjay Tyagi
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Single Molecule ◽  
Single Cells ◽  
Global Changes ◽  
Messenger Rnas ◽  
Histone Acetyl Transferase ◽  
Gene Expression Noise ◽  
Expression Noise ◽  
Eukaryotic Genes

Many eukaryotic genes are expressed in randomly initiated bursts that are punctuated by periods of quiescence. Here, we show that the intermittent access of the promoters to transcription factors through relatively impervious chromatin contributes to this “noisy” transcription. We tethered a nuclease-deficient Cas9 fused to a histone acetyl transferase at the promoters of two endogenous genes in HeLa cells. An assay for transposase-accessible chromatin using sequencing showed that the activity of the histone acetyl transferase altered the chromatin architecture locally without introducing global changes in the nucleus and rendered the targeted promoters constitutively accessible. We measured the gene expression variability from the gene loci by performing single-molecule fluorescence in situ hybridization against mature messenger RNAs (mRNAs) and by imaging nascent mRNA molecules present at active gene loci in single cells. Because of the increased accessibility of the promoter to transcription factors, the transcription from two genes became less noisy, even when the average levels of expression did not change. In addition to providing evidence for chromatin accessibility as a determinant of the noise in gene expression, our study offers a mechanism for controlling gene expression noise which is otherwise unavoidable.

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