scholarly journals Control of gene expression by glucocorticoid hormones

1984 ◽  
Vol 224 (1) ◽  
pp. 1-12 ◽  
Author(s):  
G G Rousseau
Keyword(s):  
Gene Expression ◽  
Transcription Initiation ◽  
Control Of Gene Expression ◽  
Mouse Mammary Tumour Virus ◽  
Virus Rna ◽  
Molecular Determinants ◽  
Chromatin Proteins ◽  
Modulation Of Gene Expression ◽  
Inducible Genes ◽  
Heterologous Cell

Glucocorticoids control the expression of a small number of transcriptionally active genes by increasing or decreasing mRNA concentration. Either effect can result from a transcriptional or a post-transcriptional mechanism. Induction of mouse mammary tumour virus RNA results from a stimulation of transcription initiation and depends on the presence of defined regions in proviral DNA. These regions bind the glucocorticoid receptor and behave functionally as proto-enhancers. Glucocorticoid-inducible genes can retain their sensitivity to the hormone after transfer to a heterologous cell by transfection techniques. Non-inducible genes can become inducible when linked to the promoter region of an inducible gene. The mechanisms by which the receptor-steroid complex stimulates or inhibits transcription or influences mRNA stability are unknown. Receptor binding to nucleic acids appears to be a necessary but not sufficient condition. It is likely that the receptor also interacts with chromatin proteins. This might lead to a catalytic modification of these proteins, resulting in a modulation of gene expression. Development of glucocorticoid-sensitive, biochemically defined, cell-free transcription systems should provide a tool to delineate the molecular determinants of this essential regulatory mechanism.

scholarly journals Genome organization is a major component of gene expression control in response to stress and during the cell division cycle in trypanosomes

Open Biology ◽  
2012 ◽  
Vol 2 (4) ◽  
pp. 120033 ◽  
Author(s):  
S. Kelly ◽  
S. Kramer ◽  
A. Schwede ◽  
P. K. Maini ◽  
K. Gull ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Division ◽  
Rna Polymerase Ii ◽  
Transcription Initiation ◽  
Expression Patterns ◽  
Cell Division Cycle ◽  
Control Of Gene Expression ◽  
Polycistronic Transcription ◽  
A Genome ◽  
Gene Expression Control

The trypanosome genome is characterized by RNA polymerase II-driven polycistronic transcription of protein-coding genes. Ten to hundreds of genes are co-transcribed from a single promoter; thus, selective regulation of individual genes via initiation is impossible. However, selective responses to external stimuli occur and post-transcriptional mechanisms are thought to account for all temporal gene expression patterns. We show that genes encoding mRNAs that are differentially regulated during the heat-shock response are selectively positioned in polycistronic transcription units; downregulated genes are close to transcription initiation sites and upregulated genes are distant. We demonstrate that the position of a reporter gene within a transcription unit is sufficient to reproduce this effect. Analysis of gene ontology annotations reveals that positional bias is not restricted to stress–response genes and that there is a genome-wide organization based on proximity to transcription initiation sites. Furthermore, we show that the relative abundance of mRNAs at different time points in the cell division cycle is dependent on the location of the corresponding genes to transcription initiation sites. This work provides evidence that the genome in trypanosomes is organized to facilitate co-coordinated temporal control of gene expression in the absence of selective promoters.

scholarly journals Orthogonal tuning of gene expression noise using CRISPR–Cas

2020 ◽  
Author(s):  
Fan Wu ◽  
Jiyoung Shim ◽  
Ting Gong ◽  
Cheemeng Tan
Keyword(s):  
Gene Expression ◽  
Reporter Gene ◽  
Transcription Initiation ◽  
Mrna Translation ◽  
Genetic Circuit ◽  
Control Of Gene Expression ◽  
Gene Expression Noise ◽  
Guide Rnas ◽  
Expression Noise ◽  
Genetic Components

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.

scholarly journals CRISPR Tools To Control Gene Expression in Bacteria

2020 ◽  
Vol 84 (2) ◽  
Author(s):  
Antoine Vigouroux ◽  
David Bikard
Keyword(s):  
Gene Expression ◽  
Transcription Initiation ◽  
Deep Understanding ◽  
Control Gene ◽  
Dna Breaks ◽  
Control Of Gene Expression ◽  
Activation Domains ◽  
Control Gene Expression ◽  
Common Strategy ◽  
High Throughput Screens

SUMMARY CRISPR-Cas systems have been engineered as powerful tools to control gene expression in bacteria. The most common strategy relies on the use of Cas effectors modified to bind target DNA without introducing DNA breaks. These effectors can either block the RNA polymerase or recruit it through activation domains. Here, we discuss the mechanistic details of how Cas effectors can modulate gene expression by blocking transcription initiation or acting as transcription roadblocks. CRISPR-Cas tools can be further engineered to obtain fine-tuned control of gene expression or target multiple genes simultaneously. Several caveats in using these tools have also been revealed, including off-target effects and toxicity, making it important to understand the design rules of engineered CRISPR-Cas effectors in bacteria. Alternatively, some types of CRISPR-Cas systems target RNA and could be used to block gene expression at the posttranscriptional level. Finally, we review applications of these tools in high-throughput screens and the progress and challenges in introducing CRISPR knockdown to other species, including nonmodel bacteria with industrial or clinical relevance. A deep understanding of how CRISPR-Cas systems can be harnessed to control gene expression in bacteria and build powerful tools will certainly open novel research directions.

scholarly journals General Regulatory Factors control the fidelity of transcription by restricting non-coding and ectopic initiation

2018 ◽  
Author(s):  
Drice Challal ◽  
Mara Barucco ◽  
Slawomir Kubik ◽  
Frank Feuerbach ◽  
Tito Candelli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Initiation ◽  
Essential Role ◽  
Nucleosome Positioning ◽  
List Type ◽  
Control Of Gene Expression ◽  
Regulatory Factors ◽  
Non Coding Rnas ◽  
Coding Potential ◽  
Pervasive Transcription

ABSTRACTThe fidelity of transcription initiation is essential for accurate gene expression, but the determinants of start site selection are not fully understood. Rap1 and other General Regulatory Factors (GRFs) control the expression of many genes in yeast. We show that depletion of these factors induces widespread ectopic transcription initiation within promoters. This generates many novel non-coding RNAs and transcript isoforms with diverse stability, profoundly altering the coding potential of the transcriptome. Ectopic transcription initiation strongly correlates with altered nucleosome positioning. We show that Rap1 sterically constrains nucleosomes as its mere binding to the DNA can be sufficient for restoration normal nucleosome positioning, transcription initiation and gene expression. These results demonstrate an essential role for GRFs in the fidelity of transcription initiation and in the suppression of pervasive transcription, redefining current models of their function. They have general implications for the mechanism of transcription initiation and the control of gene expression.HIGHLIGHTSRap1, Abf1 and Reb1 control the fidelity of transcription initiation and suppress pervasive transcriptionWidespread ectopic transcription initiation in Rap1-deficient cells induces variegated alterations in gene expressionAltered nucleosome positioning in GRFs-defective cells correlate with ectopic transcription initiation.Rap1 controls nucleosomes positioning and transcription initiation at least partially by a steric hindrance mechanism

A Review on Important Histone Acetyltransferase (HAT) Enzymes as Targets for Cancer Therapy

2019 ◽  
Vol 15 (2) ◽  
pp. 120-130
Author(s):  
Mohammad Ghanbari ◽  
Reza Safaralizadeh ◽  
Kiyanoush Mohammadi
Keyword(s):  
Gene Expression ◽  
Histone Acetyltransferase ◽  
Critical Role ◽  
Cancer Treatments ◽  
Control Of Gene Expression ◽  
Post Translational Modifications ◽  
Therapeutic Drugs ◽  
The Status ◽  
Acetyl Group ◽  
Increase Gene Expression

At the present time, cancer is one of the most lethal diseases worldwide. There are various factors involved in the development of cancer, including genetic factors, lifestyle, nutrition, and so on. Recent studies have shown that epigenetic factors have a critical role in the initiation and development of tumors. The histone post-translational modifications (PTMs) such as acetylation, methylation, phosphorylation, and other PTMs are important mechanisms that regulate the status of chromatin structure and this regulation leads to the control of gene expression. The histone acetylation is conducted by histone acetyltransferase enzymes (HATs), which are involved in transferring an acetyl group to conserved lysine amino acids of histones and consequently increase gene expression. On the basis of similarity in catalytic domains of HATs, these enzymes are divided into different groups such as families of GNAT, MYST, P300/CBP, SRC/P160, and so on. These enzymes have effective roles in apoptosis, signaling pathways, metastasis, cell cycle, DNA repair and other related mechanisms deregulated in cancer. Abnormal activation of HATs leads to uncontrolled amplification of cells and incidence of malignancy signs. This indicates that HAT might be an important target for effective cancer treatments, and hence there would be a need for further studies and designing of therapeutic drugs on this basis. In this study, we have reviewed the important roles of HATs in different human malignancies.

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