scholarly journals A novel mathematical method for disclosing oscillations in gene transcription: a comparative study

2017 ◽  
Author(s):  
Athanasios C. Antoulas ◽  
Bokai Zhu ◽  
Qiang Zhang ◽  
Brian York ◽  
Bert W. O'Malley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Transcription ◽  
Visual Inspection ◽  
Alternative Methods ◽  
Circadian Cycle ◽  
Regulatory Effect ◽  
Dark Cycle ◽  
Physiologic Function ◽  
Oscillatory Gene Expression ◽  
Identification Techniques

Circadian rhythmicity, the 24-hour cycle responsive to light and dark, is determined by periodic oscillations in gene transcription. This phenomenon has broad ramifications in physiologic function. Recent work has disclosed more cycles in gene transcription, and to the uncovering of these we apply a novel signal processing methodology known as the pencil method and compare it to conventional parametric, nonparametric, and statistical methods. Methods: In order to assess periodicity of gene expression over time, we analyzed a database derived from livers of mice entrained to a 12-hour light/12-hour dark cycle. We also analyzed artificially generated signals to identify differences between the pencil decomposition and other alternative methods. Results: The pencil decomposition revealed hitherto-unsuspected oscillations in gene transcription with 12-hour periodicity. The pencil method was robust in detecting the 24-hour circadian cycle that was known to exist, as well as confirming the existence of shorter-period oscillations. A key consequence of this approach is that orthogonality of the different oscillatory components can be demonstrated. thus indicating a biological independence of these oscillations, that has been subsequently confirmed empirically by knocking out the gene responsible for the 24-hour clock. Conclusion: System identification techniques can be applied to biological systems and can uncover important characteristics that may elude visual inspection of the data. Significance: The pencil method provides new insights on the essence of gene expression and discloses a wide variety of oscillations in addition to the well-studied circadian pattern. This insight opens the door to the study of novel mechanisms by which oscillatory gene expression signals exert their regulatory effect on cells to influence human diseases.

scholarly journals Gene Expression Space Shapes the Bioprocess Trade-Offs among Titer, Yield and Productivity

2021 ◽  
Vol 11 (13) ◽  
pp. 5859
Author(s):  
Fernando N. Santos-Navarro ◽  
Yadira Boada ◽  
Alejandro Vignoni ◽  
Jesús Picó
Keyword(s):  
Gene Expression ◽  
Gene Transcription ◽  
Performance Metrics ◽  
Cell Mass ◽  
Gene Copy ◽  
Substrate Uptake ◽  
Promoter Strength ◽  
Expression Levels ◽  
Trade Offs ◽  
Wide Range

Optimal gene expression is central for the development of both bacterial expression systems for heterologous protein production, and microbial cell factories for industrial metabolite production. Our goal is to fulfill industry-level overproduction demands optimally, as measured by the following key performance metrics: titer, productivity rate, and yield (TRY). Here we use a multiscale model incorporating the dynamics of (i) the cell population in the bioreactor, (ii) the substrate uptake and (iii) the interaction between the cell host and expression of the protein of interest. Our model predicts cell growth rate and cell mass distribution between enzymes of interest and host enzymes as a function of substrate uptake and the following main lab-accessible gene expression-related characteristics: promoter strength, gene copy number and ribosome binding site strength. We evaluated the differential roles of gene transcription and translation in shaping TRY trade-offs for a wide range of expression levels and the sensitivity of the TRY space to variations in substrate availability. Our results show that, at low expression levels, gene transcription mainly defined TRY, and gene translation had a limited effect; whereas, at high expression levels, TRY depended on the product of both, in agreement with experiments in the literature.

Nitric oxide increases IL-8 gene transcription and mRNA stability to enhance IL-8 gene expression in lung epithelial cells

2004 ◽  
Vol 287 (4) ◽  
pp. L764-L773 ◽  
Author(s):  
Loretta Sparkman ◽  
Vijayakumar Boggaram
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
Gene Transcription ◽  
Mrna Stability ◽  
Inflammatory Responses ◽  
Lung Epithelial Cells ◽  
Mrna Levels ◽  
Lung Epithelial

Interleukin (IL)-8, a C-X-C chemokine, is a potent chemoattractant and an activator for neutrophils, T cells, and other immune cells. The airway and respiratory epithelia play important roles in the initiation and modulation of inflammatory responses via production of cytokines and surfactant. The association between elevated levels of nitric oxide (NO) and IL-8 in acute lung injury associated with sepsis, acute respiratory distress syndrome, respiratory syncytial virus infection in infants, and other inflammatory diseases suggested that NO may play important roles in the control of IL-8 gene expression in the lung. We investigated the role of NO in the control of IL-8 gene expression in H441 lung epithelial cells. We found that a variety of NO donors significantly induced IL-8 mRNA levels, and the increase in IL-8 mRNA was associated with an increase in IL-8 protein. NO induction of IL-8 mRNA was due to increases in IL-8 gene transcription and mRNA stability. NO induction of IL-8 mRNA levels was not inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and KT-5823, inhibitors of soluble guanylate cyclase and protein kinase G, respectively, and 8-bromo-cGMP did not increase IL-8 mRNA levels. This indicated that NO induces IL-8 mRNA levels independently of changes in the intracellular cGMP levels. NO induction of IL-8 mRNA was significantly reduced by inhibitors of extracellular regulated kinase and protein kinase C. IL-8 induction by NO was also reduced by hydroxyl radical scavengers such as dimethyl sulfoxide and dimethylthiourea, indicating the involvement of hydroxyl radicals in the induction process. NO induction of IL-8 gene expression could be a significant contributing factor in the initiation and induction of inflammatory response in the respiratory epithelium.

scholarly journals Feedback Inhibition of Human Scavenger Receptor Class B Type I Gene Expression by Glucocorticoid in Adrenal and Ovarian Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 3214-3224 ◽  
Author(s):  
Sofia Mavridou ◽  
Maria Venihaki ◽  
Olga Rassouli ◽  
Christos Tsatsanis ◽  
Dimitris Kardassis
Keyword(s):  
Gene Expression ◽  
Gene Transcription ◽  
Feedback Inhibition ◽  
Steroid Hormone ◽  
Scavenger Receptor ◽  
Type I ◽  
Mrna Levels ◽  
Ovarian Cells ◽  
Scavenger Receptor Class ◽  
Class B

Scavenger receptor class B type I (SR-BI) facilitates the reverse transport of excess cholesterol from peripheral tissues to the liver via high-density lipoproteins. In steroidogenic tissues, SR-BI supplies cholesterol for steroid hormone production. We show here that the transcription of the human SR-BI gene is subject to feedback inhibition by glucocorticoid in adrenal and ovarian cells. SR-BI mRNA levels were increased in adrenals from corticosterone-insufficient Crh−/− mice, whereas corticosterone replacement by oral administration inhibited SR-BI gene expression in these mice. SR-BI mRNA levels were increased in adrenals from wild-type mice treated with metyrapone, a drug that blocks corticosterone synthesis. Experiments in adrenocortical H295R and ovarian SKOV-3 cells using cycloheximide and siRNA-mediated gene silencing revealed that glucocorticoid-mediated inhibition of SR-BI gene transcription requires de novo protein synthesis and the glucocorticoid receptor (GR). No direct binding of GR to the SR-BI promoter could be demonstrated in vitro and in vivo, suggesting an indirect mechanism of repression of SR-BI gene transcription by GR in adrenal cells. Deletion analysis established that the region of the human SR-BI promoter between nucleotides −201 and −62 is sufficient to mediate repression by glucocorticoid. This region contains putative binding sites for transcriptional repressors that could play a role in SR-BI gene regulation in response to glucocorticoid. In summary, this is the first report showing that glucocorticoid suppress SR-BI expression suggesting that steroidogenic tissues maintain steroid hormone homeostasis by prohibiting SR-BI-mediated high-density lipoprotein cholesterol uptake when the endogenous levels of glucocorticoid are elevated.

scholarly journals Signal Transducer and Activator of Transcription (Stat) 5b-Mediated Inhibition of Insulin-Like Growth Factor Binding Protein-1 Gene Transcription: A Mechanism for Repression of Gene Expression by Growth Hormone

2007 ◽  
Vol 21 (6) ◽  
pp. 1443-1457 ◽  
Author(s):  
Mitsuru Ono ◽  
Dennis J. Chia ◽  
Roxana Merino-Martinez ◽  
Amilcar Flores-Morales ◽  
Terry G. Unterman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Gene Transcription ◽  
Binding Protein ◽  
Critical Role ◽  
Somatic Growth ◽  
Transcript Profiling ◽  
Signal Transducer ◽  
Igf Binding ◽  
Igf Binding Protein

Abstract GH plays a central role in controlling somatic growth, tissue regeneration, and intermediary metabolism in most vertebrate species through mechanisms dependent on the regulation of gene expression. Recent studies using transcript profiling have identified large cohorts of genes whose expression is induced by GH. Other results have demonstrated that signal transducer and activator of transcription (Stat) 5b, a latent transcription factor activated by the GH receptor-associated protein kinase, Jak2, is a key agent in the GH-stimulated gene activation that leads to somatic growth. By contrast, little is known about the steps through which GH-initiated signaling pathways reduce gene expression. Here we show that Stat5b plays a critical role in the GH-regulated inhibition of IGF binding protein-1 gene transcription by impairing the actions of the FoxO1 transcription factor on the IGF binding protein-1 promoter. Additional observations using transcript profiling in the liver indicate that Stat5b may be a general mediator of GH-initiated gene repression. Our results provide a model for understanding how GH may simultaneously stimulate and inhibit the expression of different cohorts of genes via the same transcription factor, potentially explaining how GH action leads to integrated biological responses in the whole organism.

Role of heat shock transcription factor in yeast metallothionein gene expression

1991 ◽  
Vol 11 (7) ◽  
pp. 3676-3681
Author(s):  
W M Yang ◽  
W Gahl ◽  
D Hamer
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Heat Shock ◽  
Gene Transcription ◽  
Heat Shock Factor ◽  
Heat Shock Transcription Factor ◽  
Wild Type ◽  
Promoter Sequences ◽  
Metallothionein Gene ◽  
Upstream Promoter

The induction of Saccharomyces cerevisiae metallothionein gene transcription by Cu and Ag is mediated by the ACE1 transcription factor. In an effort to detect additional stimuli and factors that regulate metallothionein gene transcription, we isolated a Cu-resistant suppressor mutant of an ACE1 deletion strain. Even in the absence of metals, the suppressor mutant exhibited high basal levels of metallothionein gene transcription that required upstream promoter sequences. The suppressor gene was cloned, and its predicted product was shown to correspond to yeast heat shock transcription factor with a single-amino-acid substitution in the DNA-binding domain. The mutant heat shock factor bound strongly to metallothionein gene upstream promoter sequences, whereas wild-type heat shock factor interacted weakly with the same region. Heat treatment led to a slight but reproducible induction of metallothionein gene expression in both wild-type and suppressor strains, and Cd induced transcription in the mutant strain. These studies provide evidence for multiple pathways of metallothionein gene transcriptional regulation in S. cerevisiae.

Comparison of Papanicolaou Test With Visual Detection Tests in Screening for Cervical Cancer and Developing the Optimal Strategy for Low Resource Settings

2010 ◽  
Vol 20 (5) ◽  
pp. 862-868 ◽  
Author(s):  
Pakhee Aggarwal ◽  
Swaraj Batra ◽  
Gauri Gandhi ◽  
Vijay Zutshi
Keyword(s):  
Cervical Cancer ◽  
Predictive Value ◽  
Visual Inspection ◽  
Visual Detection ◽  
Alternative Methods ◽  
Papanicolaou Test ◽  
Low Resource Settings ◽  
Low Resource ◽  
The Mean ◽  
Sensitivity Specificity

Objectives:To compare the sensitivity, specificity, positive and negative predictive values, and accuracy of Papanicolaou test with visual inspection with acetic acid (VIA)/VIA using magnification devices (VIAM) and develop the best strategy for screening in low resource settings.Materials and Methods:This is a prospective cross-sectional study on 408 symptomatic multiparous women in the reproductive age group, sequentially using the Papanicolaou test, the VIA, and the VIAM for screening. Women with a positive screening test underwent guided biopsy and endocervical curettage. The site of biopsy was recorded. Histopathological findings were taken as the "gold" standard in comparing the methods.Results:The mean (SD) age was 32.3 (6.8) years (range, 15-49 years), whereas the mean (SD) parity was 2.9 (1.2) (range, 1-9). Abnormal cytological findings were detected in 2.9% patients, whereas the remaining smears were negative for any intraepithelial lesion or malignancy. A total of 113 cases were screened positive by one/all methods. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the Papanicolaou test, the VIA, and the VIAM were 24, 98, 42, 96, and 94%; 95, 78, 19, 99, and 79%; and 95, 78, 19, 99, and 79%, respectively, for high-grade lesions.Conclusions:The Papanicolaou test had low sensitivity but high specificity, whereas visual detection methods had a high sensitivity in addition to being cheaper. Alternative methods of screening such as VIA/VIAM can be a valuable alternative to the Papanicolaou test for cervical cancer screening in low resource settings. Visual inspection using magnification devices may be of benefit over VIA in doubtful cases.

scholarly journals Regulation of GLUT5 gene expression in rat intestinal mucosa: regional distribution, circadian rhythm, perinatal development and effect of diabetes

1995 ◽  
Vol 309 (1) ◽  
pp. 271-277 ◽  
Author(s):  
A Castelló ◽  
A Gumá ◽  
L Sevilla ◽  
M Furriols ◽  
X Testar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Intestine ◽  
Circadian Rhythm ◽  
Intestinal Absorption ◽  
Light Period ◽  
Proximal Jejunum ◽  
Mrna Levels ◽  
Dark Cycle ◽  
Perinatal Development ◽  
Streptozotocin Induced Diabetes

1. GLUT5 gene expression was studied in small intestine under a variety of conditions characterized by altered intestinal absorption of monosaccharides. 2. RNA-blotting studies showed that GLUT5 mRNA was abundantly expressed in rat and rabbit intestine and kidney, but it was not detected in heart or brown adipose tissue. GLUT5 mRNA levels were higher in the upper segments of the small intestine (duodenum and proximal jejunum) than in the lower segments (distal jejunum and ileum). 3. The intestinal expression of GLUT5 mRNA in rat proximal jejunum showed circadian rhythm. A 12-fold increase in GLUT5 mRNA levels was detected at the end of the light cycle and at the beginning of the dark cycle when compared with the early light period. In keeping with this, GLUT5 protein content in brush-border membranes was also increased at the beginning of the dark cycle compared with that in the light period. 4. In streptozotocin-induced diabetes an 80% increase in GLUT5 mRNA levels in mucosa from the proximal jejunum was detected under conditions in which enhanced intestinal absorption of monosaccharides has been reported. 5. The intestinal expression of GLUT5 mRNA showed regulation during perinatal development. Levels of GLUT5 mRNA were low during fetal life, increased progressively during the postnatal period and reached levels comparable with the adult state after weaning. Weaning on to a high-fat diet partially prevented the induction of GLUT5 gene expression. 6. Our results indicate that GLUT5 gene expression is tightly regulated in small intestine. Regulation involves maximal expression in the upper part of the small intestine, circadian rhythm, developmental regulation dependent on the fat and carbohydrate content in the diet at weaning and enhanced expression in streptozotocin-induced diabetes. Furthermore, changes observed in intestinal GLUT5 expression correlate with reported alterations in intestinal absorption of fructose. This suggests a regulatory role for GLUT5 in fructose uptake by absorptive enterocytes.

scholarly journals Spaceflight Induces Novel Regulatory Responses in Arabidopsis Seedling as Revealed by Combined Proteomic and Transcriptomic Analyses

2020 ◽  
Author(s):  
Colin Peter Singer Kruse ◽  
Alexander D Meyers ◽  
Proma Basu ◽  
Sarahann Hutchinson ◽  
Darron R Luesse ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Wall ◽  
Membrane Proteins ◽  
Plant Growth ◽  
Gene Transcription ◽  
Space Station ◽  
Growth Efficiency ◽  
Rna Seq ◽  
Plastid Gene ◽  
The Impact

Abstract Background: Understanding of gravity sensing and response is critical to long-term human habitation in space and can provide new advantages for terrestrial agriculture. To this end, the altered gene expression profile induced by microgravity has been repeatedly queried by microarray and RNA-seq experiments to understand gravitropism. However, the quantification of altered protein abundance in space has been minimally investigated. Results: Proteomic (iTRAQ-labelled LC-MS/MS) and transcriptomic (RNA-seq) analyses simultaneously quantified protein and transcript differential expression of three-day old, etiolated Arabidopsis thaliana seedlings grown aboard the International Space Station along with their ground control counterparts. Protein extracts were fractionated to isolate soluble and membrane proteins and analyzed to detect differentially phosphorylated peptides. In total, 968 RNAs, 107 soluble proteins, and 103 membrane proteins were identified as differentially expressed. In addition, the proteomic analyses identified 16 differential phosphorylation events. Proteomic data delivered novel insights and simultaneously provided new context to previously made observations of gene expression in microgravity. There is a sweeping shift in post-transcriptional mechanisms of gene regulation including RNA-decapping protein DCP5, the splicing factors GRP7 and GRP8, and AGO4,. These data also indicate AHA2 and FERONIA as well as CESA1 and SHOU4 as central to the cell wall adaptations seen in spaceflight. Patterns of tubulin-a 1, 3,4 and 6 phosphorylation further reveal an interaction of microtubule and redox homeostasis that mirrors osmotic response signaling elements. The absence of gravity also results in a seemingly wasteful dysregulation of plastid gene transcription. Conclusions: The datasets gathered from Arabidopsis seedlings exposed to microgravity revealed marked impacts on post-transcriptional regulation, cell wall synthesis, redox/microtubule dynamics, and plastid gene transcription. The impact of post-transcriptional regulatory alterations represents an unstudied element of the plant microgravity response with the potential to significantly impact plant growth efficiency and beyond. What’s more, addressing the effects of microgravity on AHA2, CESA1, and alpha tubulins has the potential to enhance cytoskeletal organization and cell wall composition, thereby enhancing biomass production and growth in microgravity. Finally, understanding and manipulating the dysregulation of plastid gene transcription has further potential to address the goal of enhancing plant growth in the stressful conditions of microgravity.

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