scholarly journals Translational control of gene expression noise and its relationship to ageing in yeast

FEBS Journal ◽  
2020 ◽  
Author(s):  
Tailise Carolina de Souza‐Guerreiro ◽  
Xiang Meng ◽  
Estelle Dacheux ◽  
Helena Firczuk ◽  
John McCarthy
2020 ◽  
Author(s):  
Fan Wu ◽  
Jiyoung Shim ◽  
Ting Gong ◽  
Cheemeng Tan

Abstract The control of gene expression noise is important for improving drug treatment and the performance of synthetic biological systems. Previous work has tuned gene expression noise by changing the rate of transcription initiation, mRNA degradation, and mRNA translation. However, these methods are invasive: they require changes to the target genetic components. Here, we create an orthogonal system based on CRISPR-dCas9 to tune gene expression noise. Specifically, we modulate the gene expression noise of a reporter gene in Escherichia coli by incorporating CRISPR activation and repression (CRISPRar) simultaneously in a single cell. The CRISPRar uses a single dCas9 that recognizes two different single guide RNAs (sgRNA). We build a library of sgRNA variants with different expression activation and repression strengths. We find that expression noise and mean of a reporter gene can be tuned independently by CRISPRar. Our results suggest that the expression noise is tuned by the competition between two sgRNAs that modulate the binding of RNA polymerase to promoters. The CRISPRar may change how we tune expression noise at the genomic level. Our work has broad impacts on the study of gene functions, phenotypical heterogeneity, and genetic circuit control.


2020 ◽  
Vol 11 ◽  
Author(s):  
Michael Tyler Guinn ◽  
Yiming Wan ◽  
Sarah Levovitz ◽  
Dongbo Yang ◽  
Marsha R. Rosner ◽  
...  

2021 ◽  
Vol 118 (42) ◽  
pp. e2018640118
Author(s):  
LaTasha C. R. Fraser ◽  
Ryan J. Dikdan ◽  
Supravat Dey ◽  
Abhyudai Singh ◽  
Sanjay Tyagi

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.


2005 ◽  
Vol 135 (3) ◽  
pp. 367-375 ◽  
Author(s):  
Ali K. Reiter ◽  
Stephen J. Crozier ◽  
Scot R. Kimball ◽  
Leonard S. Jefferson

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