scholarly journals Inferring gene regulation dynamics from static snapshots of gene expression variability

2021 ◽  
Vol 104 (4) ◽  
Author(s):  
Euan Joly-Smith ◽  
Zitong Jerry Wang ◽  
Andreas Hilfinger
2020 ◽  
Author(s):  
Benjamin J. Fair ◽  
Lauren E. Blake ◽  
Abhishek Sarkar ◽  
Bryan J. Pavlovic ◽  
Claudia Cuevas ◽  
...  

AbstractInter-individual variation in gene expression has been shown to be heritable and it is often associated with differences in disease susceptibility between individuals. Many studies focused on mapping associations between genetic and gene regulatory variation, yet much less attention has been paid to the evolutionary processes that shape the observed differences in gene regulation between individuals in humans or any other primate. To begin addressing this gap, we performed a comparative analysis of gene expression variability and expression quantitative trait loci (eQTLs) in humans and chimpanzees, using gene expression data from primary heart samples. We found that expression variability in both species is often determined by non-genetic sources, such as cell-type heterogeneity. However, we also provide evidence that inter-individual variation in gene regulation can be genetically controlled, and that the degree of such variability is generally conserved in humans and chimpanzees. In particular, we found a significant overlap of orthologous genes associated with eQTLs in both species. We conclude that gene expression variability in humans and chimpanzees often evolves under similar evolutionary pressures.


2020 ◽  
Vol 11 ◽  
Author(s):  
Sandra Cortijo ◽  
Marcel Bhattarai ◽  
James C. W. Locke ◽  
Sebastian E. Ahnert

Co-expression networks are a powerful tool to understand gene regulation. They have been used to identify new regulation and function of genes involved in plant development and their response to the environment. Up to now, co-expression networks have been inferred using transcriptomes generated on plants experiencing genetic or environmental perturbation, or from expression time series. We propose a new approach by showing that co-expression networks can be constructed in the absence of genetic and environmental perturbation, for plants at the same developmental stage. For this, we used transcriptomes that were generated from genetically identical individual plants that were grown under the same conditions and for the same amount of time. Twelve time points were used to cover the 24-h light/dark cycle. We used variability in gene expression between individual plants of the same time point to infer a co-expression network. We show that this network is biologically relevant and use it to suggest new gene functions and to identify new targets for the transcriptional regulators GI, PIF4, and PRR5. Moreover, we find different co-regulation in this network based on changes in expression between individual plants, compared to the usual approach requiring environmental perturbation. Our work shows that gene co-expression networks can be identified using variability in gene expression between individual plants, without the need for genetic or environmental perturbations. It will allow further exploration of gene regulation in contexts with subtle differences between plants, which could be closer to what individual plants in a population might face in the wild.


2018 ◽  
Author(s):  
Dirk Benzinger ◽  
Mustafa Khammash

Many natural transcription factors are regulated in a pulsatile fashion, but it remains unknown whether synthetic gene expression systems can benefit from such dynamic regulation. Using a fast-acting, light-responsive transcription factor in Saccharomyces cerevisiae, we show that dynamic pulsatile signals reduce cell-to-cell variability in gene expression. We then show that by encoding such signals into a single input, expression mean and variability can be precisely and independently tuned. Further, we construct a light-responsive promoter library and demonstrate how pulsatile signaling also enables graded multi-gene regulation at fixed expression ratios, despite differences in promoter dose-response characteristics. Pulsatile regulation can thus lead to highly beneficial functional behaviors in synthetic biological systems, which previously required laborious optimization of genetic parts or complex construction of synthetic gene networks.


2020 ◽  
Author(s):  
S Cortijo ◽  
M Bhattarai ◽  
J C W Locke ◽  
S E Ahnert

AbstractCo-expression networks are a powerful tool to understand gene regulation. They have been used to identify new regulation and function of genes involved in plant development and their response to the environment. Up to now, co-expression networks have been inferred using transcriptomes generated on plants experiencing genetic or environmental perturbation, or from expression time series. We propose a new approach by showing that co-expression networks can be constructed in the absence of genetic and environmental perturbation, for plants at the same developmental stage. For this we used transcriptomes that were generated from genetically identical individual plants that were grown in the same conditions and for the same amount of time. Twelve time points were used to cover the 24h light/dark cycle. We used variability in gene expression between individual plants of the same time point to infer a co-expression network. We show that this network is biologically relevant and use it to suggest new gene functions and to identify new targets for the transcription factors GI, PIF4 and PRR5. Moreover, we find different co-regulation in this network based on changes in expression between individual plants, compared to the usual approach requiring environmental perturbation. Our work shows that gene co-expression networks can be identified using variability in gene expression between individual plants, without the need for genetic or environmental perturbations. It will allow further exploration of gene regulation in contexts with subtle differences between plants, which could be closer to what individual plants in a population might face in the wild.Author summaryPlant development and response to changes in the environment are strongly regulated at the level of gene expression. That is why understanding how gene expression is regulated is key, and transcriptome approaches have allowed the analysis of transcription for all genes of the genome. Extracting useful information from the high amount of data generated by transcriptomes is a challenge, and gene co-expression networks are a powerful tool to do this. The principle is to find genes that co-vary in expression in different conditions and to pair them together. Communities of genes that are more closely linked are then identified and this is the starting point to look for their implication in the same pathway. Co-expression networks have been used to identify new regulation and function of genes involved in plant development and their response to the environment. They were constructed using transcriptomes generated on plants experiencing genetic or environmental perturbation. We show that co-expression networks can in fact be constructed in the absence of genetic and environmental perturbation. Our work will allow further exploration of gene co-regulation in contexts with subtle differences between plants, which could be closer to what individual plants in a population might face in the wild.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Benjamin Jung Fair ◽  
Lauren E Blake ◽  
Abhishek Sarkar ◽  
Bryan J Pavlovic ◽  
Claudia Cuevas ◽  
...  

Inter-individual variation in gene expression has been shown to be heritable and is often associated with differences in disease susceptibility between individuals. Many studies focused on mapping associations between genetic and gene regulatory variation, yet much less attention has been paid to the evolutionary processes that shape the observed differences in gene regulation between individuals in humans or any other primate. To begin addressing this gap, we performed a comparative analysis of gene expression variability and expression quantitative trait loci (eQTLs) in humans and chimpanzees, using gene expression data from primary heart samples. We found that expression variability in both species is often determined by non-genetic sources, such as cell-type heterogeneity. However, we also provide evidence that inter-individual variation in gene regulation can be genetically controlled, and that the degree of such variability is generally conserved in humans and chimpanzees. In particular, we found a significant overlap of orthologous genes associated with eQTLs in both species. We conclude that gene expression variability in humans and chimpanzees often evolves under similar evolutionary pressures.


2013 ◽  
Vol 40 (12) ◽  
pp. 1256
Author(s):  
XiaoDong JIA ◽  
XiuJie CHEN ◽  
Xin WU ◽  
JianKai XU ◽  
FuJian TAN ◽  
...  

2021 ◽  
Vol 22 (6) ◽  
pp. 3234
Author(s):  
Juhyun Lee ◽  
Si-Eun Sung ◽  
Janghyun Lee ◽  
Jin Young Kang ◽  
Joon-Hwa Lee ◽  
...  

Riboswitches are segments of noncoding RNA that bind with metabolites, resulting in a change in gene expression. To understand the molecular mechanism of gene regulation in a fluoride riboswitch, a base-pair opening dynamics study was performed with and without ligands using the Bacillus cereus fluoride riboswitch. We demonstrate that the structural stability of the fluoride riboswitch is caused by two steps depending on ligands. Upon binding of a magnesium ion, significant changes in a conformation of the riboswitch occur, resulting in the greatest increase in their stability and changes in dynamics by a fluoride ion. Examining hydrogen exchange dynamics through NMR spectroscopy, we reveal that the stabilization of the U45·A37 base-pair due to the binding of the fluoride ion, by changing the dynamics while maintaining the structure, results in transcription regulation. Our results demonstrate that the opening dynamics and stabilities of a fluoride riboswitch in different ion states are essential for the genetic switching mechanism.


2021 ◽  
Vol 22 (5) ◽  
pp. 2599
Author(s):  
Mégane Collobert ◽  
Ozvan Bocher ◽  
Anaïs Le Nabec ◽  
Emmanuelle Génin ◽  
Claude Férec ◽  
...  

About 8% of the human genome is covered with candidate cis-regulatory elements (cCREs). Disruptions of CREs, described as “cis-ruptions” have been identified as being involved in various genetic diseases. Thanks to the development of chromatin conformation study techniques, several long-range cystic fibrosis transmembrane conductance regulator (CFTR) regulatory elements were identified, but the regulatory mechanisms of the CFTR gene have yet to be fully elucidated. The aim of this work is to improve our knowledge of the CFTR gene regulation, and to identity factors that could impact the CFTR gene expression, and potentially account for the variability of the clinical presentation of cystic fibrosis as well as CFTR-related disorders. Here, we apply the robust GWAS3D score to determine which of the CFTR introns could be involved in gene regulation. This approach highlights four particular CFTR introns of interest. Using reporter gene constructs in intestinal cells, we show that two new introns display strong cooperative effects in intestinal cells. Chromatin immunoprecipitation analyses further demonstrate fixation of transcription factors network. These results provide new insights into our understanding of the CFTR gene regulation and allow us to suggest a 3D CFTR locus structure in intestinal cells. A better understand of regulation mechanisms of the CFTR gene could elucidate cases of patients where the phenotype is not yet explained by the genotype. This would thus help in better diagnosis and therefore better management. These cis-acting regions may be a therapeutic challenge that could lead to the development of specific molecules capable of modulating gene expression in the future.


Sign in / Sign up

Export Citation Format

Share Document