scholarly journals Gene by Environment Interactions reveal new regulatory aspects of signaling network plasticity

PLoS Genetics ◽  
2022 ◽  
Vol 18 (1) ◽  
pp. e1009988
Author(s):  
Matthew D. Vandermeulen ◽  
Paul J. Cullen
Keyword(s):  
Target Genes ◽  
Invasive Growth ◽  
Integrated Networks ◽  
Regulatory Pathways ◽  
Complex Phenotypes ◽  
Gene By Environment Interactions ◽  
Powerful Approach ◽  
Pathway Regulation ◽  
Regulated Gene Expression ◽  
High Degree

Phenotypes can change during exposure to different environments through the regulation of signaling pathways that operate in integrated networks. How signaling networks produce different phenotypes in different settings is not fully understood. Here, Gene by Environment Interactions (GEIs) were used to explore the regulatory network that controls filamentous/invasive growth in the yeast Saccharomyces cerevisiae. GEI analysis revealed that the regulation of invasive growth is decentralized and varies extensively across environments. Different regulatory pathways were critical or dispensable depending on the environment, microenvironment, or time point tested, and the pathway that made the strongest contribution changed depending on the environment. Some regulators even showed conditional role reversals. Ranking pathways’ roles across environments revealed an under-appreciated pathway (OPI1) as the single strongest regulator among the major pathways tested (RAS, RIM101, and MAPK). One mechanism that may explain the high degree of regulatory plasticity observed was conditional pathway interactions, such as conditional redundancy and conditional cross-pathway regulation. Another mechanism was that different pathways conditionally and differentially regulated gene expression, such as target genes that control separate cell adhesion mechanisms (FLO11 and SFG1). An exception to decentralized regulation of invasive growth was that morphogenetic changes (cell elongation and budding pattern) were primarily regulated by one pathway (MAPK). GEI analysis also uncovered a round-cell invasion phenotype. Our work suggests that GEI analysis is a simple and powerful approach to define the regulatory basis of complex phenotypes and may be applicable to many systems.

scholarly journals Pleiotropic and Epistatic Network-Based Discovery: Integrated Networks for Target Gene Discovery

2018 ◽  
Author(s):  
Deborah Weighill ◽  
Piet Jones ◽  
Manesh Shah ◽  
Priya Ranjan ◽  
Wellington Muchero ◽  
...  
Keyword(s):  
Target Genes ◽  
Genome Wide Association Study ◽  
Populus Trichocarpa ◽  
Lignin Biosynthesis ◽  
Cellular Functions ◽  
Integrated Networks ◽  
Network Layers ◽  
Complex Phenotypes ◽  
Genome Wide ◽  
Lines Of Evidence

AbstractBiological organisms are complex systems that are composed of functional networks of interacting molecules and macromolecules. Complex phenotypes are the result of orchestrated, hierarchical, heterogeneous collections of expressed genomic variants. However, the effects of these variants are the result of historic selective pressure and current environmental and epigenetic signals, and, as such, their co-occurrence can be seen as genome-wide correlations in a number of different manners. Biomass recalcitrance (i.e., the resistance of plants to degradation or deconstruction, which ultimately enables access to a plant’s sugars) is a complex polygenic phenotype of high importance to biofuels initiatives. This study makes use of data derived from the re-sequenced genomes from over 800 different Populus trichocarpa genotypes in combination with metabolomic and pyMBMS data across this population, as well as co-expression and co-methylation networks in order to better understand the molecular interactions involved in recalcitrance, and identify target genes involved in lignin biosynthesis/degradation. A Lines Of Evidence (LOE) scoring system is developed to integrate the information in the different layers and quantify the number of lines of evidence linking genes to lignin-related lignin-phenotypes across the network layers. The resulting Genome Wide Association Study networks, integrated with Single Nucleotide Polymorphism (SNP) correlation, co-methylation and co-expression networks through the LOE scores are proving to be a powerful approach to determine the pleiotropic and epistatic relationships underlying cellular functions and, as such, the molecular basis for complex phenotypes, such as recalcitrance.

scholarly journals Key Regulatory Pathways, MicroRNAs, and Target Genes Participate in Adventitious Root Formation of Acer Rubrum L

2021 ◽  
Author(s):  
Wenpeng Zhu ◽  
Manyu Zhang ◽  
Jianyi Li ◽  
Hewen Zhao ◽  
Kezhong Zhang ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Seedling Survival ◽  
Expression Patterns ◽  
Economic Value ◽  
Acer Rubrum ◽  
Pcr Analysis ◽  
Asexual Propagation ◽  
Regulatory Pathways

Abstract BackgroundAcer rubrum L. is a colorful ornamental tree with great economic value. Because this tree is difficult to root under natural conditions and the seedling survival rate is low, vegetative propagation methods are often used. Because the formation of adventitious roots (ARs) is essential for the survival of asexual propagation of A. rubrum, it is necessary to investigate the molecular regulatory mechanisms in the formation of ARs of A. ruburm. To address this knowledge gap, we sequenced the transcriptome and sRNA of the A. rubrum variety ‘Autumn Fantasy’ using high-throughput sequencing and explored changes in gene and microRNA (miRNA) expression in response to exogenous auxin treatment. ResultsWe identified 82,468 differentially expressed genes between the treated and untreated ARs, as well as 48 known and 95 novel miRNAs. We also identified 172 target genes of the known miRNAs using degradome sequencing. Two regulatory pathways (ubiquitin mediated proteolysis and plant hormone signal transduction), Ar-miR160a and the target gene ArARF10 were shown to be involved in the auxin response. We further investigated the expression patterns and regulatory roles of ArARF10 through subcellular localization, transcriptional activation, plant transformation, qRT-PCR analysis, and GUS staining. ConclusionsDifferential expression patterns indicated the Ar-miR160a-ArARF10 interaction might play a significant role in the regulation of AR formation in A. rubrum. Our study provided new insights into mechanisms underlying the regulation of AR formation in A. rubrum.

scholarly journals Identification of the Q Gene Playing a Role in Spike Morphology Variation in Wheat Mutants and Its Regulatory Network

2022 ◽  
Vol 12 ◽  
Author(s):  
Jiazi Zhang ◽  
Hongchun Xiong ◽  
Huijun Guo ◽  
Yuting Li ◽  
Xiaomei Xie ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Expression Patterns ◽  
Spike Morphology ◽  
Regulatory Pathways ◽  
Dynamic Expression ◽  
Spike Development ◽  
Family Gene ◽  
Q Gene

The wheat AP2 family gene Q controls domestication traits, including spike morphology and threshability, which are critical for the widespread cultivation and yield improvement of wheat. Although many studies have investigated the molecular mechanisms of the Q gene, its direct target genes, especially those controlling spike morphology, are not clear, and its regulatory pathways are not well established. In this study, we conducted gene mapping of a wheat speltoid spike mutant and found that a new allele of the Q gene with protein truncation played a role in spike morphology variation in the mutant. Dynamic expression levels of the Q gene throughout the spike development process suggested that the transcript abundances of the mutant were decreased at the W6 and W7 scales compared to those of the WT. We identified several mutation sites on the Q gene and showed that mutations in different domains resulted in distinct phenotypes. In addition, we found that the Q gene produced three transcripts via alternative splicing and that they exhibited differential expression patterns in nodes, internodes, flag leaves, and spikes. Finally, we identified several target genes directly downstream of Q, including TaGRF1-2D and TaMGD-6B, and proposed a possible regulatory network. This study uncovered the target genes of Q, and the results can help to clarify the mechanism of wheat spike morphology and thereby improve wheat grain yield.

scholarly journals Smad Proteins and Hepatocyte Growth Factor Control Parallel Regulatory Pathways That Converge on β1-Integrin To Promote Normal Liver Development

2001 ◽  
Vol 21 (15) ◽  
pp. 5122-5131 ◽  
Author(s):  
Michael Weinstein ◽  
Satdarshan P. S. Monga ◽  
Ye Liu ◽  
Steven G. Brodie ◽  
Yi Tang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Type I ◽  
Β1 Integrin ◽  
Adhesive Properties ◽  
Regulatory Pathways ◽  
Smad Proteins ◽  
Hepatocyte Growth

ABSTRACT Smads serve as intracellular mediators of transforming growth factor β (TGF-β) signaling. After phosphorylation by activated type I TGF-β receptors, Smad proteins translocate to the nucleus, where they serve as transcription factors and increase or decrease expression of TGF-β target genes. Mice lacking one copy each ofSmad2 and Smad3 suffered midgestation lethality due to liver hypoplasia and anemia, suggesting essential dosage requirements of TGF-β signal components. This is likely due to abnormal adhesive properties of the mutant hepatocytes, which may result from a decrease in the level of the β1-integrin and abnormal processing and localization of E-cadherin. Culture of mutant livers in vitro revealed the existence of a parallel developmental pathway mediated by hepatocyte growth factor (HGF), which could rescue the mutant phenotype independent of Smad activation. These pathways merge at the β1-integrin, the level of which was increased by HGF in the cultured mutant livers. HGF treatment reversed the defects in cell proliferation and hepatic architecture in theSmad2 +/− ; Smad3 +/− livers.

scholarly journals Expression of plasmid DNA in the salivary gland epithelium: novel approaches to study dynamic cellular processes in live animals

2009 ◽  
Vol 297 (6) ◽  
pp. C1347-C1357 ◽  
Author(s):  
Monika Sramkova ◽  
Andrius Masedunskas ◽  
Laura Parente ◽  
Alfredo Molinolo ◽  
Roberto Weigert
Keyword(s):  
Plasmid Dna ◽  
Target Genes ◽  
Specific Cell ◽  
Experimental Conditions ◽  
Live Animal ◽  
Cellular Processes ◽  
Submandibular Salivary Glands ◽  
Powerful Approach ◽  
Approaches To Study ◽  
Granular Ducts

The ability to dynamically image cellular and subcellular structures in a live animal and to target genes to a specific cell population in a living tissue provides a unique tool to address many biological questions in the proper physiological context. Here, we describe a powerful approach that is based on the use of rat submandibular salivary glands, which offer the possibility to easily perform intravital imaging and deliver molecules from the oral cavity, and plasmid DNA, which offers the advantage of rapid manipulations. We show that, under different experimental conditions, a reporter molecule can be rapidly expressed in specific compartments of the glands: 1) in the intercalated ducts, when plasmid DNA is administered alone, and 2) in granular ducts, striated ducts, and, to a lesser extent, acini, when plasmid DNA is mixed with replication-deficient adenovirus subtype 5 particles. Remarkably, we also found that gene expression can be directed to acinar cells when plasmid DNA is administered during isoproterenol-stimulated exocytosis, suggesting a novel mechanism of plasmid internalization regulated by compensatory endocytosis. Finally, as a practical application of these strategies, we show how the expression of fluorescently tagged molecules enables the study of the dynamics of various organelles in live animals at a resolution comparable to that achieved in cell cultures.

scholarly journals Differentially Expressed miRNAs in Tumor, Adjacent, and Normal Tissues of Lung Adenocarcinoma

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Fei Tian ◽  
Rui Li ◽  
Zhenzhu Chen ◽  
Yanting Shen ◽  
Jiafeng Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Target Genes ◽  
Expression Profiles ◽  
Major Type ◽  
Regulatory Pathways ◽  
Normal Tissues ◽  
Qrt Pcr ◽  
Diagnosis And Prognosis ◽  
Tumor Tissues

Lung cancer is the leading cause of cancer deaths. Non-small-cell lung cancer (NSCLC) is the major type of lung cancer. The aim of this study was to characterize the expression profiles of miRNAs in adenocarcinoma (AC), one major subtype of NSCLC. In this study, the miRNAs were detected in normal, adjacent, and tumor tissues by next-generation sequencing. Then the expression levels of differential miRNAs were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In the results, 259, 401, and 389 miRNAs were detected in tumor, adjacent, and normal tissues of pooled AC samples, respectively. In addition, for the first time we have found that miR-21-5p and miR-196a-5p were gradually upregulated from normal to adjacent to tumor tissues; miR-218-5p was gradually downregulated with 2-fold or greater change in AC tissues. These 3 miRNAs were validated by qRT-PCR. Lastly, we predicted target genes of these 3 miRNAs and enriched the potential functions and regulatory pathways. The aberrant miR-21-5p, miR-196a-5p, and miR-218-5p may become biomarkers for diagnosis and prognosis of lung adenocarcinoma. This research may be useful for lung adenocarcinoma diagnosis and the study of pathology in lung cancer.

scholarly journals The TEA Transcription Factor Tec1 Confers Promoter-Specific Gene Regulation by Ste12-Dependent and -Independent Mechanisms

2010 ◽  
Vol 9 (4) ◽  
pp. 514-531 ◽  
Author(s):  
Barbara Heise ◽  
Julia van der Felden ◽  
Sandra Kern ◽  
Mario Malcher ◽  
Stefan Brückner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Target Genes ◽  
Specific Gene ◽  
Dependent Manner ◽  
A Genome ◽  
Regulated Gene Expression

ABSTRACT In Saccharomyces cerevisiae, the TEA transcription factor Tec1 is known to regulate target genes together with a second transcription factor, Ste12. Tec1-Ste12 complexes can activate transcription through Tec1 binding sites (TCSs), which can be further combined with Ste12 binding sites (PREs) for cooperative DNA binding. However, previous studies have hinted that Tec1 might regulate transcription also without Ste12. Here, we show that in vivo, physiological amounts of Tec1 are sufficient to stimulate TCS-mediated gene expression and transcription of the FLO11 gene in the absence of Ste12. In vitro, Tec1 is able to bind TCS elements with high affinity and specificity without Ste12. Furthermore, Tec1 contains a C-terminal transcriptional activation domain that confers Ste12-independent activation of TCS-regulated gene expression. On a genome-wide scale, we identified 302 Tec1 target genes that constitute two distinct classes. A first class of 254 genes is regulated by Tec1 in a Ste12-dependent manner and is enriched for genes that are bound by Tec1 and Ste12 in vivo. In contrast, a second class of 48 genes can be regulated by Tec1 independently of Ste12 and is enriched for genes that are bound by the stress transcription factors Yap6, Nrg1, Cin5, Skn7, Hsf1, and Msn4. Finally, we find that combinatorial control by Tec1-Ste12 complexes stabilizes Tec1 against degradation. Our study suggests that Tec1 is able to regulate TCS-mediated gene expression by Ste12-dependent and Ste12-independent mechanisms that enable promoter-specific transcriptional control.

scholarly journals The Unfolded Protein Response Regulates Multiple Aspects of Secretory and Membrane Protein Biogenesis and Endoplasmic Reticulum Quality Control

2000 ◽  
Vol 150 (1) ◽  
pp. 77-88 ◽  
Author(s):  
Davis T.W. Ng ◽  
Eric D. Spear ◽  
Peter Walter
Keyword(s):  
Membrane Protein ◽  
Unfolded Protein Response ◽  
Intracellular Signaling ◽  
Target Genes ◽  
Yeast Saccharomyces Cerevisiae ◽  
Regulatory Pathways ◽  
Unfolded Protein ◽  
Protein Biogenesis ◽  
The Unfolded Protein Response ◽  
Protein Response

The unfolded protein response (UPR) is an intracellular signaling pathway that relays signals from the lumen of the ER to activate target genes in the nucleus. We devised a genetic screen in the yeast Saccharomyces cerevisiae to isolate mutants that are dependent on activation of the pathway for viability. Using this strategy, we isolated mutants affecting various aspects of ER function, including protein translocation, folding, glycosylation, glycosylphosphatidylinositol modification, and ER-associated protein degradation (ERAD). Extending results gleaned from the genetic studies, we demonstrate that the UPR regulates trafficking of proteins at the translocon to balance the needs of biosynthesis and ERAD. The approach also revealed connections of the UPR to other regulatory pathways. In particular, we identified SON1/RPN4, a recently described transcriptional regulator for genes encoding subunits of the proteasome. Our genetic strategy, therefore, offers a powerful means to provide insight into the physiology of the UPR and to identify novel genes with roles in many aspects of secretory and membrane protein biogenesis.

Glucocorticoid hormones and energy homeostasis

2014 ◽  
Vol 19 (2) ◽  
Author(s):  
Roldan M. de Guia ◽  
Adam J. Rose ◽  
Stephan Herzig
Keyword(s):  
Energy Homeostasis ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Metabolic Dysfunction ◽  
Endocrine Control ◽  
Regulatory Pathways ◽  
Glucose And Lipid Metabolism ◽  
Steroid Binding

AbstractGlucocorticoids (GC) and their cognate intracellular receptor, the glucocorticoid receptor (GR), have been characterised as critical checkpoints in the endocrine control of energy homeostasis in mammals. Indeed, aberrant GC action has been linked to a variety of severe metabolic diseases, including obesity, insulin resistance and type 2 diabetes. As a steroid-binding member of the nuclear receptor superfamily of transcription factors, the GR translocates into the cell nucleus upon GC binding where it serves as a transcriptional regulator of distinct GC-responsive target genes that are – in many cases – associated with glucose and lipid regulatory pathways and thereby intricately control both physiological and pathophysiological systemic energy homeostasis. Here, we summarize the current knowledge of GC/GR function in energy metabolism and systemic metabolic dysfunction, particularly focusing on glucose and lipid metabolism.

Microarray analyses of SREBP-1a and SREBP-1c target genes identify new regulatory pathways in muscle

2008 ◽  
Vol 34 (3) ◽  
pp. 327-337 ◽  
Author(s):  
Sophie Rome ◽  
Virginie Lecomte ◽  
Emmanuelle Meugnier ◽  
Jennifer Rieusset ◽  
Cyrille Debard ◽  
...  
Keyword(s):  
Target Genes ◽  
Cholesterol Metabolism ◽  
Regulatory Element ◽  
Mrna Level ◽  
Primary Cultures ◽  
Muscle Cells ◽  
Binding Motif ◽  
Regulatory Pathways ◽  
Human Skeletal Muscle Cells ◽  
Sterol Regulatory Element

In this study we have identified the target genes of sterol regulatory element binding protein (SREBP)-1a and SREBP-1c in primary cultures of human skeletal muscle cells, using adenoviral vectors expressing the mature nuclear form of human SREBP-1a or SREBP-1c combined with oligonucleotide microarrays. Overexpression of SREBP-1a led to significant changes in the expression of 1,315 genes (655 upregulated and 660 downregulated), whereas overexpression of SREBP-1c modified the mRNA level of 514 genes (310 upregulated and 204 downregulated). Gene ontology analysis indicated that in human muscle cells SREBP-1a and -1c are involved in the regulation of a large number of genes that are at the crossroads of different functional pathways, several of which are not directly connected with cholesterol and lipid metabolism. Six hundred fifty-two of all genes identified to be differentially regulated on SREBP overexpression had a sterol regulatory element (SRE) motif in their promoter sequences. Among these, 429 were specifically regulated by SREBP-1a, 69 by SREBP-1c, and 154 by both 1a and 1c. Because both isoforms recognize the same binding motif, we determined whether some of these functional differences could depend on the environment of the SRE motifs in the promoters. Results from promoter analysis showed that different combinations of transcription factor binding sites around the SRE binding motifs may determine regulatory networks of transcription that could explain the superposition of lipid and cholesterol metabolism with various other pathways involved in adaptive responses to stress like hypoxia and heat shock, or involvement in the immune response.

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