scholarly journals Molecular mechanisms of genetic variation and transcriptional regulation of CYP2C19

2012 ◽  
Vol 3 ◽  
Author(s):  
Nuala Ann Helsby ◽  
Kathryn Elisa Burns
Keyword(s):  
Genetic Variation ◽  
Transcriptional Regulation ◽  
Molecular Mechanisms

scholarly journals The ETS-Domain Transcription Factor Elk-1 Regulates COX-2 Gene Expression and Inhibits Glucose-Stimulated Insulin Secretion in the Pancreaticβ-Cell Line INS-1

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Xiong-Fei Zhang ◽  
Yi Zhu ◽  
Wen-Biao Liang ◽  
Jing-Jing Zhang
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Regulation ◽  
Insulin Secretion ◽  
Cell Line ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Cell Dysfunction ◽  
Cox 2 ◽  
Glucose Stimulated Insulin Secretion

Cyclooxygenase-2 (COX-2) expression is associated with many aspects of physiological and pathological conditions, including pancreaticβ-cell dysfunction. Prostaglandin E2 (PGE2) production, as a consequence of COX-2 gene induction, has been reported to impairβ-cell function. The molecular mechanisms involved in the regulation of COX-2 gene expression are not fully understood. We previously demonstrated that transcription factor Elk-1 significantly upregulated COX-2 gene promoter activity. In this report, we used pancreaticβ-cell line (INS-1) to explore the relationships between Elk-1 and COX-2. We first investigated the effects of Elk-1 on COX-2 transcriptional regulation and expression in INS-1 cells. We thus undertook to study the binding of Elk-1 to its putative binding sites in the COX-2 promoter. We also analysed glucose-stimulated insulin secretion (GSIS) in INS-1 cells that overexpressed Elk-1. Our results demonstrate that Elk-1 efficiently upregulates COX-2 expression at least partly through directly binding to the −82/−69 region of COX-2 promoter. Overexpression of Elk-1 inhibits GSIS in INS-1 cells. These findings will be helpful for better understanding the transcriptional regulation of COX-2 in pancreaticβ-cell. Moreover, Elk-1, the transcriptional regulator of COX-2 expression, will be a potential target for the prevention ofβ-cell dysfunction mediated by PGE2.

Molecular mechanisms of transcriptional regulation by the nuclear zinc-finger protein Zfat in T cells

2016 ◽  
Vol 1859 (11) ◽  
pp. 1398-1410 ◽  
Author(s):  
Shuhei Ishikura ◽  
Toshiyuki Tsunoda ◽  
Kazuhiko Nakabayashi ◽  
Keiko Doi ◽  
Midori Koyanagi ◽  
...  
Keyword(s):  
T Cells ◽  
Transcriptional Regulation ◽  
Zinc Finger ◽  
Molecular Mechanisms ◽  
Zinc Finger Protein ◽  
Finger Protein

scholarly journals Transcriptional regulation in model organisms: recent progress and clinical implications

Open Biology ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 190183 ◽  
Author(s):  
Jiaqi Tang ◽  
Zhenhua Xu ◽  
Lianfang Huang ◽  
Hui Luo ◽  
Xiao Zhu
Keyword(s):  
Transcriptional Regulation ◽  
Molecular Mechanisms ◽  
The Body ◽  
Model Organisms ◽  
Clinical Implications ◽  
Regulation Mechanism ◽  
Biological Behaviour ◽  
E Coli ◽  
Different Types

In this review, we will summarize model organisms used by scientists in the laboratory, including Escherichia coli , yeast, Arabidopsis thaliana , nematodes, Drosophila , zebrafish, mice and other animals. We focus on the progress in research exploring different types of E. coli in the human body, and the specific molecular mechanisms by which they play a role in humans. First, we discuss the specific transcriptional regulation mechanism of E. coli in cell development, maturation, ageing and longevity, as well as tumorigenesis and development. Then, we discuss how the synthesis of some important substances in cells is regulated and how this affects biological behaviour. Understanding and applying these mechanisms, presumably, can greatly improve the quality of people's lives as well as increase their lifespan. For example, some E. coli can activate certain cells by secreting insulin-like growth factor-1, thus activating the inflammatory response of the body, while other E. coli can inactivate the immune response of the body by secreting toxic factors.

The roles of post-translational modifications and coactivators of STAT6 signaling in tumor growth and progression

2020 ◽  
Vol 12 (21) ◽  
pp. 1945-1960
Author(s):  
Hao Huang ◽  
Yizhou Zheng ◽  
Linfu Li ◽  
Weimei Shi ◽  
Rui Zhang ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Tumor Growth ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Structural Characteristics ◽  
Tumor Development ◽  
Metastatic Tumors ◽  
Post Translational Modifications ◽  
Signal Transducers ◽  
Development And Management

Signal transducers and activators of transcription 6 (STAT6) are highly expressed in various tumors and associated with tumorigenesis, immunosuppression, proliferation, metastasis and poor prognosis in human cancers. In response to IL-4/13, STAT6 is phosphorylated, dimerizes and triggers transcriptional regulation after recruitment of coactivators to transcriptosome, such as CBP/p300, SRC-1, PARP-14 and PSF. Post-translational modifications, including phosphorylation, ubiquitination, ADP-ribosylation and acetylation, have been explored for molecular mechanisms of STAT6 in tumor development and management. STAT6 has been developed as a specific biomarker for distinguishing and diagnosing tumor phenotypes, although it is observed to be frequently mutated in metastatic tumors. In this article, we focus mainly on the structural characteristics of STAT6 and its role in tumor growth and progression.

scholarly journals Ethylene regulates post-germination seedling growth in wheat through spatial and temporal modulation of ABA/GA balance

2019 ◽  
Vol 71 (6) ◽  
pp. 1985-2004 ◽  
Author(s):  
Menghan Sun ◽  
Pham Anh Tuan ◽  
Marta S Izydorczyk ◽  
Belay T Ayele
Keyword(s):  
Transcriptional Regulation ◽  
Seedling Growth ◽  
Molecular Mechanisms ◽  
Starch Degradation ◽  
Aba Signaling ◽  
Temporal Modulation ◽  
Aba Metabolism ◽  
Radicle Protrusion ◽  
Storage Starch

Abstract This study aimed to gain insights into the molecular mechanisms underlying the role of ethylene in regulating germination and seedling growth in wheat by combining pharmacological, molecular, and metabolomics approaches. Our study showed that ethylene does not affect radicle protrusion but controls post-germination endospermic starch degradation through transcriptional regulation of specific α-amylase and α-glucosidase genes, and this effect is mediated by alteration of endospermic bioactive gibberellin (GA) levels, and GA sensitivity via expression of the GA signaling gene, TaGAMYB. Our data implicated ethylene as a positive regulator of embryo axis and coleoptile growth through transcriptional regulation of specific TaEXPA genes. These effects were associated with modulation of GA levels and sensitivity, through expression of GA metabolism (TaGA20ox1, TaGA3ox2, and TaGA2ox6) and signaling (TaGAMYB) genes, respectively, and/or the abscisic acid (ABA) level and sensitivity, via expression of specific ABA metabolism (TaNCED2 or TaCYP707A1) and signaling (TaABI3) genes, respectively. Ethylene appeared to regulate the expression of TaEXPA3 and thereby root growth through its control of coleoptile ABA metabolism, and root ABA signaling via expression of TaABI3 and TaABI5. These results show that spatiotemporal modulation of ABA/GA balance mediates the role of ethylene in regulating post-germination storage starch degradation and seedling growth in wheat.

scholarly journals Additive genetic variation of transcriptional regulation: metallothionein expression in the soil insect Orchesella cincta

Heredity ◽  
2005 ◽  
Vol 96 (1) ◽  
pp. 85-92 ◽  
Author(s):  
D Roelofs ◽  
L Overhein ◽  
M E de Boer ◽  
T K S Janssens ◽  
N M van Straalen
Keyword(s):  
Genetic Variation ◽  
Transcriptional Regulation ◽  
Additive Genetic Variation ◽  
Orchesella Cincta

Transcriptional regulation of phosphate transporters from Lolium perenne and its mycorrhizal symbionts in response to phosphorus supply

2015 ◽  
Vol 42 (1) ◽  
pp. 1 ◽  
Author(s):  
Qianhe Liu ◽  
Anthony J. Parsons ◽  
Hong Xue ◽  
Chris S. Jones ◽  
Susanne Rasmussen
Keyword(s):  
Transcriptional Regulation ◽  
Lolium Perenne ◽  
Molecular Mechanisms ◽  
Arbuscular Mycorrhizal ◽  
P Uptake ◽  
P Availability ◽  
Pasture Grass ◽  
Transcript Levels ◽  
Soil P ◽  
Mycorrhizal Colonisation

Phosphate (P) uptake is critical for plant growth, but to date little is known about P uptake and transport in the pasture grass Lolium perenne L. We have identified a putative P transporter (PT) from L. perenne mycorrhizal roots (LpPT1) and assessed its transcriptional regulation by soil P availability and mycorrhizal colonisation. We also investigated transcript levels of fungal PTs from the two arbuscular mycorrhizal species Rhizophagus intraradices and Funneliformis mosseae. Our analyses indicated that LpPT1 codes for a high affinity PT most likely responsible for direct P uptake from the soil. LpPT1 is highly expressed in roots of plants grown at low P, whereas high P repressed its expression. LpPT1 was not expressed in above-ground plant tissues. Colonisation with R. intraradices did not affect expression of LpPT1 significantly. Transcript levels of the R. intraradices PT were not affected by P availability but the F. mosseae PT was repressed by high P supply, particularly in intraradical hyphae. Our study could assist in deciphering the molecular mechanisms of P uptake in the pasture grass L. perenne.

scholarly journals Evidence for Transcriptome-wide RNA Editing Among Sus scrofa PRE-1 SINE Elements

2017 ◽  
Author(s):  
Scott A. Funkhouser ◽  
Juan P. Steibel ◽  
Ronald O. Bates ◽  
Nancy E. Raney ◽  
Darius Schenk ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Transcriptional Regulation ◽  
Rna Editing ◽  
High Throughput ◽  
Sus Scrofa ◽  
Sequence Data ◽  
Rna Sequences ◽  
Editing Event ◽  
Coding Regions ◽  
Dna And Rna

AbstractBackgroundRNA editing by ADAR (adenosine deaminase acting on RNA) proteins is a form of transcriptional regulation that is widespread among humans and other primates. Based on high-throughput scans used to identify putative RNA editing sites, ADAR appears to catalyze a substantial number of adenosine to inosine transitions within repetitive regions of the primate transcriptome, thereby dramatically enhancing genetic variation beyond what is encoded in the genome.ResultsHere, we demonstrate the editing potential of the pig transcriptome by utilizing DNA and RNA sequence data from the same pig. We identified a total of 8550 mismatches between DNA and RNA sequences across three tissues, with 75% of these exhibiting an A-to-G (DNA to RNA) discrepancy, indicative of a canonical ADAR-catalyzed RNA editing event. When we consider only mismatches within repetitive regions of the genome, the A-to-G percentage increases to 94%, with the majority of these located within the swine specific SINE retrotransposon PRE-1. We also observe evidence of A-to-G editing within coding regions that were previously verified in primates.ConclusionsThus, our high-throughput evidence suggests that pervasive RNA editing by ADAR can exist outside of the primate lineage to dramatically enhance genetic variation in pigs.

scholarly journals A novel quantile regression approach for eQTL discovery

2016 ◽  
Author(s):  
Xiaoyu Song ◽  
Gen Li ◽  
Iuliana Ionita-Laza ◽  
Ying Wei
Keyword(s):  
Gene Expression ◽  
Genetic Variation ◽  
Linear Regression ◽  
Genetic Variants ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Expression Level ◽  
Special Focus ◽  
Genome Wide Association Studies ◽  
Genome Wide

AbstractOver the past decade, there has been a remarkable improvement in our understanding of the role of genetic variation in complex human diseases, especially via genome-wide association studies. However, the underlying molecular mechanisms are still poorly characterized, impending the development of therapeutic interventions. Identifying genetic variants that influence the expression level of a gene, i.e. expression quantitative trait loci (eQTLs), can help us understand how genetic variants influence traits at the molecular level. While most eQTL studies focus on identifying mean effects on gene expression using linear regression, evidence suggests that genetic variation can impact the entire distribution of the expression level. Indeed, several studies have already investigated higher order associations with a special focus on detecting heteroskedasticity. In this paper, we develop a Quantile Rank-score Based Test (QRBT) to identify eQTLs that are associated with the conditional quantile functions of gene expression. We have applied the proposed QRBT to the Genotype-Tissue Expression project, an international tissue bank for studying the relationship between genetic variation and gene expression in human tissues, and found that the proposed QRBT complements the existing methods, and identifies new eQTLs with heterogeneous effects genome-wideacross different quantile levels. Notably, we show that the eQTLs identified by QRBT but missed by linear regression are more likely to be tissue specific, and also associated with greater enrichment in genome-wide significant SNPs from the GWAS catalog. An R package implementing QRBT is available on our website.

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