scholarly journals Mycoplasma stress response: adaptive regulation or broken brakes?

2014 ◽  
Author(s):  
Pavel V Mazin ◽  
Gleb Y Fisunov ◽  
Alexey Y Gorbachev ◽  
Ilya A Altukhov ◽  
Tatiana A Semashko ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Regulation ◽  
Core Promoter ◽  
Bacterial Pathogen ◽  
Rna Seq ◽  
Transcriptional Responses ◽  
Transcription Start Sites ◽  
False Discovery ◽  
Almost All ◽  
Gene Expression Levels

The avian bacterial pathogen Mycoplasma gallisepticum is a good model for transcriptional regulation studies due to its small genome and relative simplicity. In this study, we used RNA-Seq experiments combined with MS-based proteomics to accurately map coding sequences (CDSs), transcription start sites (TSSs) and transcription terminators (TTs) and to decipher their roles in stress-induced transcriptional responses. We identified 1061 TSSs at an FDR (false discovery rate) of 10% and showed that almost all transcription in M. gallisepticum is initiated from classic TATAAT promoters, which are surrounded by A/T-rich sequences and rarely accompanied by a -35 element. Our analysis revealed the pronounced complexity of the operon structure: on average, each coding operon has one internal TSS and TT in addition to the primary ones. Our new transcriptomic approach based on the intervals between the two closest transcription initiators and/or terminators allowed us to identify two classes of TTs: strong, unregulated and hairpin-containing TTs and weak, heat shock-regulated and hairpinless TTs. Comparing the gene expression levels under different conditions (such as heat, osmotic and peroxide stresses) revealed widespread and divergent transcription regulation in M. gallisepticum. Modeling suggested that the structure of the core promoter plays a major role in gene expression regulation. We have shown that the heat stress activation of cryptic promoters combined with the suppression of hairpinless TTs leads to widespread, seemingly non-functional transcription.

scholarly journals High heterogeneity undermines generalization of differential expression results in RNA-Seq analysis

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Weitong Cui ◽  
Huaru Xue ◽  
Lei Wei ◽  
Jinghua Jin ◽  
Xuewen Tian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Expression ◽  
Small Sample ◽  
Differentially Expressed ◽  
Cancer Type ◽  
Rna Seq ◽  
Sample Sizes ◽  
Large Sample ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Background RNA sequencing (RNA-Seq) has been widely applied in oncology for monitoring transcriptome changes. However, the emerging problem that high variation of gene expression levels caused by tumor heterogeneity may affect the reproducibility of differential expression (DE) results has rarely been studied. Here, we investigated the reproducibility of DE results for any given number of biological replicates between 3 and 24 and explored why a great many differentially expressed genes (DEGs) were not reproducible. Results Our findings demonstrate that poor reproducibility of DE results exists not only for small sample sizes, but also for relatively large sample sizes. Quite a few of the DEGs detected are specific to the samples in use, rather than genuinely differentially expressed under different conditions. Poor reproducibility of DE results is mainly caused by high variation of gene expression levels for the same gene in different samples. Even though biological variation may account for much of the high variation of gene expression levels, the effect of outlier count data also needs to be treated seriously, as outlier data severely interfere with DE analysis. Conclusions High heterogeneity exists not only in tumor tissue samples of each cancer type studied, but also in normal samples. High heterogeneity leads to poor reproducibility of DEGs, undermining generalization of differential expression results. Therefore, it is necessary to use large sample sizes (at least 10 if possible) in RNA-Seq experimental designs to reduce the impact of biological variability and DE results should be interpreted cautiously unless soundly validated.

scholarly journals Genetic effect in leaf and xylem transcriptome variations among Eucalyptus urophylla x grandis hybrids in field conditions

2018 ◽  
Vol 67 (1) ◽  
pp. 57-65
Author(s):  
Alexandre Vaillant ◽  
Astrid Honvault ◽  
Stéphanie Bocs ◽  
Maryline Summo ◽  
Garel Makouanzi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Variance Components ◽  
Genetic Effect ◽  
Field Conditions ◽  
Eucalyptus Urophylla ◽  
Rna Seq ◽  
Intermediate Phenotypes ◽  
False Discovery ◽  
Hybrid Clones ◽  
Selection Of

Abstract To assess the genetic and environmental components of gene-expression variation among trees we used RNA-seq technology and Eucalyptus urophylla x grandis hybrid clones tested in field conditions. Leaf and xylem transcriptomes of three 20 month old clones differing in terms of growth, repeated in two blocks, were investigated. Transcriptomes were very similar between ramets. The number of expressed genes was significantly (P<0.05) higher in leaf (25,665±634) than in xylem (23,637±1,241). A pairwise clone comparisons approach showed that 4.5 to 14 % of the genes were diffe­rentially expressed (false discovery rate [FDR]<0.05) in leaf and 7.1 to 16 % in xylem. An assessment of among clone variance components revealed significant results in leaf and xylem in 3431 (248) genes (at FDR<0.2) and 160 (3) (at FDR<0.05), respectively. These two complementary approa­ches displayed correlated results. A focus on the phenylpro­panoid, cellulose and xylan pathways revealed a large majo­rity of low expressed genes and a few highly expressed ones, with RPKM values ranging from nearly 0 to 600 in leaf and 10,000 in xylem. Out of the 115 genes of these pathways, 45 showed differential expression for at least one pair of geno­type, five of which displaying also clone variance compo­nents. These preliminary results are promising in evaluating whether gene expression can serve as possible ‘intermediate phenotypes’ that could improve the accuracy of selection of grossly observable traits.

scholarly journals Gene Expression Does Not Support the Developmental Hourglass Model in Three Animals with Spiralian Development

2019 ◽  
Vol 36 (7) ◽  
pp. 1373-1383 ◽  
Author(s):  
Longjun Wu ◽  
Kailey E Ferger ◽  
J David Lambert
Keyword(s):  
Gene Expression ◽  
Large Fraction ◽  
Molecular Data ◽  
Development Stage ◽  
Data Sets ◽  
Rna Seq ◽  
Developmental Evolution ◽  
Phylotypic Stage ◽  
Hourglass Model ◽  
Almost All

Abstract It has been proposed that animals have a pattern of developmental evolution resembling an hourglass because the most conserved development stage—often called the phylotypic stage—is always in midembryonic development. Although the topic has been debated for decades, recent studies using molecular data such as RNA-seq gene expression data sets have largely supported the existence of periods of relative evolutionary conservation in middevelopment, consistent with the phylotypic stage and the hourglass concepts. However, so far this approach has only been applied to a limited number of taxa across the tree of life. Here, using established phylotranscriptomic approaches, we found a surprising reverse hourglass pattern in two molluscs and a polychaete annelid, representatives of the Spiralia, an understudied group that contains a large fraction of metazoan body plan diversity. These results suggest that spiralians have a divergent midembryonic stage, with more conserved early and late development, which is the inverse of the pattern seen in almost all other organisms where these phylotranscriptomic approaches have been reported. We discuss our findings in light of proposed reasons for the phylotypic stage and hourglass model in other systems.

scholarly journals Association of intronic DNA methylation and hydroxymethylation alterations in the epigenetic etiology of dilated cardiomyopathy

2019 ◽  
Vol 317 (1) ◽  
pp. H168-H180 ◽  
Author(s):  
Ali M. Tabish ◽  
Mohammed Arif ◽  
Taejeong Song ◽  
Zaher Elbeck ◽  
Richard C. Becker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dilated Cardiomyopathy ◽  
Cardiac Remodeling ◽  
Rna Seq ◽  
Wild Type ◽  
Kegg Pathways ◽  
Wild Type Phenotype ◽  
Gene Expression Levels

In this study, we investigated the role of DNA methylation [5-methylcytosine (5mC)] and 5-hydroxymethylcytosine (5hmC), epigenetic modifications that regulate gene activity, in dilated cardiomyopathy (DCM). A MYBPC3 mutant mouse model of DCM was compared with wild type and used to profile genomic 5mC and 5hmC changes by Chip-seq, and gene expression levels were analyzed by RNA-seq. Both 5mC-altered genes (957) and 5hmC-altered genes (2,022) were identified in DCM hearts. Diverse gene ontology and KEGG pathways were enriched for DCM phenotypes, such as inflammation, tissue fibrosis, cell death, cardiac remodeling, cardiomyocyte growth, and differentiation, as well as sarcomere structure. Hierarchical clustering of mapped genes affected by 5mC and 5hmC clearly differentiated DCM from wild-type phenotype. Based on these data, we propose that genomewide 5mC and 5hmC contents may play a major role in DCM pathogenesis. NEW & NOTEWORTHY Our data demonstrate that development of dilated cardiomyopathy in mice is associated with significant epigenetic changes, specifically in intronic regions, which, when combined with gene expression profiling data, highlight key signaling pathways involved in pathological cardiac remodeling and heart contractile dysfunction.

scholarly journals Pathogenic Biohacking: Induction, Modulation and Subversion of Host Transcriptional Responses by Listeria monocytogenes

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 294
Author(s):  
Matthew J. G. Eldridge ◽  
Pascale Cossart ◽  
Mélanie A. Hamon
Keyword(s):  
Gene Expression ◽  
Listeria Monocytogenes ◽  
Virulence Factors ◽  
Bacterial Pathogen ◽  
Typical Feature ◽  
Host Gene ◽  
Host Cells ◽  
Host Gene Expression ◽  
Transcriptional Responses ◽  
The Impact

During infection, the foodborne bacterial pathogen Listeria monocytogenes dynamically influences the gene expression profile of host cells. Infection-induced transcriptional changes are a typical feature of the host-response to bacteria and contribute to the activation of protective genes such as inflammatory cytokines. However, by using specialized virulence factors, bacterial pathogens can target signaling pathways, transcription factors, and epigenetic mechanisms to alter host gene expression, thereby reprogramming the response to infection. Therefore, the transcriptional profile that is established in the host is delicately balanced between antibacterial responses and pathogenesis, where any change in host gene expression might significantly influence the outcome of infection. In this review, we discuss the known transcriptional and epigenetic processes that are engaged during Listeria monocytogenes infection, the virulence factors that can remodel them, and the impact these processes have on the outcome of infection.

scholarly journals Among family variation in survival and gene expression uncovers adaptive genetic variation in a threatened fish

2019 ◽  
Author(s):  
Avril M. Harder ◽  
Janna R. Willoughby ◽  
William R. Ardren ◽  
Mark R. Christie
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Atlantic Salmon ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Adaptive Genetic Variation ◽  
Transcriptional Responses ◽  
Survival Analyses ◽  
Thiamine Treatment ◽  
Family Variation

AbstractVariation in among-family transcriptional responses to different environmental conditions can help to identify adaptive genetic variation, even prior to a selective event. Coupling differential gene expression with formal survival analyses allows for the disentanglement of treatment effects, required for understanding how individuals plastically respond to environmental stressors, from the adaptive genetic variation responsible for among-family variation in survival and gene expression. We applied this experimental design to investigate responses to an emerging conservation issue, thiamine (vitamin B1) deficiency, in a threatened population of Atlantic salmon (Salmo salar). Thiamine is an essential vitamin that is increasingly limited in many ecosystems. In Lake Champlain, Atlantic salmon cannot acquire thiamine in sufficient quantities to support natural reproduction; fertilized eggs must be reared in hatcheries and treated with supplemental thiamine. We evaluated transcriptional responses (RNA-seq) to thiamine treatment across families and found 3,616 genes differentially expressed between control (no supplemental thiamine) and treatment individuals. Fewer genes changed expression additively (i.e., equally among families) than non-additively (i.e., family-by-treatment effects) in response to thiamine. Differentially expressed genes were related to known physiological effects of thiamine deficiency, including oxidative stress, cardiovascular irregularities, and neurological abnormalities. We also identified 1,446 putatively adaptive genes that were strongly associated with among-family survival in the absence of thiamine treatment, many of which related to neurogenesis and visual perception. Our results highlight the utility of coupling RNA-seq with formal survival analyses to identify candidate genes that underlie the among-family variation in survival required for an adaptive response to natural selection.

scholarly journals Plant organ evolution revealed by phylotranscriptomics in Arabidopsis

2017 ◽  
Author(s):  
Li Lei ◽  
Joshua G Steffen ◽  
Edward J Osborne ◽  
Christopher Toomajian
Keyword(s):  
Gene Expression ◽  
Evolutionary History ◽  
Morphological Evolution ◽  
Sequence Divergence ◽  
Rna Seq ◽  
Plant Organ ◽  
New Perspective ◽  
Adaptive Signal ◽  
Floral Bud ◽  
Gene Expression Levels

ABSTRACTThe evolution of species’ phenotypes occurs through changes both in protein sequence and gene expression levels. Though much of plant morphological evolution can be explained by changes in gene expression, examining its evolution has challenges. To gain a new perspective on organ evolution in plants, we applied a phylotranscriptomics approach. We combined a phylostratigraphic approach with gene expression based on the strand-specific RNA-seq data from seedling, floral bud, and root of 19 Arabidopsis thaliana accessions to examine the age and sequence divergence of transcriptomes from these organs and how they adapted over time. Our results indicate that, among the sense and antisense transcriptomes of these organs, the sense transcriptomes of seedlings are the evolutionarily oldest across all accessions and are the most conserved in amino acid sequence for most accessions. In contrast, among the sense transcriptomes from these same organs, those from floral bud are evolutionarily youngest and least conserved in sequence for most accessions. Different organs have adaptive peaks at different stages in their evolutionary history, however, from the Magnoliophyta stage to the Brassicale stage, all three organs show a common adaptive signal. Our research is significant because it offers novel evolutionary insight on plant organs revealed by phylotranscriptomics.

scholarly journals An Arabidopsis gene expression predictor enables inference of transcriptional regulators

2020 ◽  
Author(s):  
Haiying Geng ◽  
Meng Wang ◽  
Jiazhen Gong ◽  
Yupu Xu ◽  
Shisong Ma
Keyword(s):  
Gene Expression ◽  
Lateral Root ◽  
Secondary Cell Wall ◽  
Target Genes ◽  
Gene Expression Regulation ◽  
Transcriptional Regulators ◽  
Endoplasmic Reticulum Stress Response ◽  
Rna Seq ◽  
Average Correlation ◽  
Cell Wall Development

ABSTRACTGene expression regulation by transcription factors (TF) has long been studied, but no model exists yet that can accurately predict transcriptome profiles based on TF activities. We have constructed a universal predictor for Arabidopsis to predict the expression of 28192 non-TF genes using 1678 TFs. Applied to bulk RNA-Seq samples from diverse tissues, the predictor produced accurate predicted transcriptomes correlating well with actual expression, with average correlation coefficient of 0.986. Having recapitulated the quantitative relationships between TFs and target genes, the predictor further enabled downstream inference of TF regulators for genes and pathways, i.e. those involved in suberin, flavonoid, glucosinolate metabolism, lateral root, xylem, secondary cell wall development, and endoplasmic reticulum stress response. Our predictor provides an innovative approach to study transcriptional regulation.

scholarly journals Using pan RNA-seq analysis to reveal the ubiquitous existence of 5’ end and 3’ end small RNAs

2018 ◽  
Author(s):  
Xiaofeng Xu ◽  
Haishuo Ji ◽  
Zhi Cheng ◽  
Xiufeng Jin ◽  
Xue Yao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Steady State ◽  
Small Rnas ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Cost Effective ◽  
Rna Degradation ◽  
Point Of View ◽  
Rna Seq ◽  
Dsrna Cleavage

AbstractIn this study, we used pan RNA-seq analysis to reveal the ubiquitous existence of 5’ end and 3’ end small RNAs. 5’ and 3’ sRNAs alone can be used to annotate mitochondrial with 1-bp resolution and nuclear non-coding genes and identify new steady-state RNAs, which are usually from functional genes. Using 5’, 3’ and intronic sRNAs, we revealed that the enzymatic dsRNA cleavage and RNAi could involve in the RNA degradation and gene expression regulation of U1 snRNA in human. The further study of 5’, 3’ and intronic sRNAs help rediscover double-stranded RNA (dsRNA) cleavage, RNA interference (RNAi) and the regulation of gene expression, which challenges the classical theories. In this study, we provided a simple and cost effective way for the annotation of mitochondrial and nuclear non-coding genes and the identification of new steady-state RNAs, particularly long non-coding RNAs (lncRNAs). We also provided a different point of view for cancer and virus, based on the new discoveries of dsRNA cleavage, RNAi and the regulation of gene expression.

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