Gcn4p-mediated transcriptional stress response
Ontology highlight
ABSTRACT:
ORGANISM(S): Schizosaccharomyces pombe Saccharomyces cerevisiae
PROVIDER: GSE4709 | GEO | 2009/02/01
SECONDARY ACCESSION(S): PRJNA95591
REPOSITORIES: GEO
Similar Datasets
Project description:The transcriptional data from an integrative analysis of transcriptional and metabolic stress responses that provides a more complete understanding of the mechanisms by which genetic regulatory circuits mediate metabolic phenotype. Experiment Overall Design: Our investigation disrupts native transcriptional control of amino acid biosynthesis via the Gcn4p- mediated transcriptional stress response. Specifically, genetic perturbation of transcriptional regulator Gcn4p in a stress condition is achieved via wild-type S288C and gcn4-delta strains in a pH-controlled chemostat environment in which a titrated inhibitor creates near histidine starvation and glucose supply limits growth to a pre-defined rate (0.10 hr^-1). The gene expression chip titles indicate the condition.
2009-02-08 | E-GEOD-4709 | biostudies-arrayexpress
Project description:Stressors during early embryogenesis influence embryo developmental trajectories and have long-term metabolic effect on offspring, but the underlying mechanism remains elusive. We performed RNA-Seq to identify transcriptional differences among control and IVF embryos. Results revealed that DNA damage and the resulting activation of Fzr1 play a central role in early embryo stress responses and subsequently affect metabolic reprogramming in offspring. To investigate the underlying molecular mechanism by which Fzr1 affected embryo development and adult metabolism. We performed RNA-Seq and H3K9me3 ChIP-seq experiments to identify transcriptional and histone modification differences among control and Fzr1-OE blastocysts. To explore the underlying mechanisms of Fzr1 activation-induced metabolic disorder, we performed RNA-Seq on the subcutaneous fat tissues of 4-month-old control and Fzr1-OE mice. We further performed reduced-representation bisulfite sequencing (RRBS) of subcutaneous fat tissues to identify possible DNA methylation alterations that could potentially mediate the intergenerational transmission of the obesity phenotype. Our findings therefore provide a new perspective on the mechanisms underlying transgenerational metabolic reprogramming and will help improve offspring health.
2023-12-31 | GSE182567 | GEO
Project description:This a model from the article:
Synthetic in vitro transcriptional oscillators.
Kim J, Winfree E Mol. Syst. Biol.
2011 Feb 1;7:465. 21283141
,
Abstract:
The construction of synthetic biochemical circuits from simple components illuminates how complex beha
viors can arise in chemistry and builds a foundation for future biological technologies. A simplified
analog of genetic regulatory networks, in vitro transcriptional circuits, provides a modular platform
for the systematic construction of arbitrary circuits and requires only two essential enzymes, bacteri
ophage T7 RNA polymerase and Escherichia coli ribonuclease H, to produce and degrade RNA signals. In t
his study, we design and experimentally demonstrate three transcriptional oscillators in vitro. First,
a negative feedback oscillator comprising two switches, regulated by excitatory and inhibitory RNA si
gnals, showed up to five complete cycles. To demonstrate modularity and to explore the design space fu
rther, a positive-feedback loop was added that modulates and extends the oscillatory regime. Finally,
a three-switch ring oscillator was constructed and analyzed. Mathematical modeling guided the design p
rocess, identified experimental conditions likely to yield oscillations, and explained the system's ro
bust response to interference by short degradation products. Synthetic transcriptional oscillators cou
ld prove valuable for systematic exploration of biochemical circuit design principles and for controll
ing nanoscale devices and orchestrating processes within artificial cells.
Note:
The paper describes 7 models (MODEL1012090000-6) and all these are submitted by the authors. This
model (MODEL1012090000) corresponds to the Simple model for both mode I and II (Design I and II).
The model reproduces timecourse figure plotted in the supplementary material (page 10 of Supplementary
material) of the reference publication.
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In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2024-09-02 | BIOMD0000000322 | BioModels
Project description:Metabolic disorders such as obesity and nonalcoholic fatty liver disease (NAFLD) are emerging disorders that affect the global population. One facet of the disorders is attributed to the disturbance of membrane lipid homeostasis. Perturbation of endoplasmic reticulum (ER) homeostasis through changes in membrane phospholipid composition results in activation of the unfolded protein response (UPR) and causes dramatic translational and transcriptional changes in cell. To restore cellular homeostasis, the three highly conserved UPR transducers ATF6, IRE1, and PERK mediate cellular processes upon ER stress. The roles of the UPR in proteostatic stress caused by the accumulation of misfolded protein is well understood but lipid perturbation-induced UPR remains elusive. We found that genetically attenuated PC synthesis in C. elegans causes lipid droplets accumulation if not for the intervention of the UPR program. Transcriptional profiling of lipid perturbation-induced ER stress animals shows a unique subset of genes modulated in an UPR-dependent manner that are unaffected by proteostatic stress. Among these, we identified IRE1-modulated autophagy genes that trigger liberation of free fatty acids from excess lipid droplets suggesting a stress release mechanism by which free fatty acids are rechannelling to restore lipid homeostasis. Considering the important role of lipid homeostasis and how its impairment contributes to the pathologies in metabolic diseases, our data uncovers the indispensable role of a fully functional UPR program in regulating lipid homeostais in the face of chronic ER stress.
2018-10-31 | GSE99763 | GEO
Project description:Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mech- anisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic dif- ferences in GR-induced transcriptional activation may mediate the risk for depression and other psy- chiatric disorders by altering a network of function- ally related stress-sensitive genes in blood and brain.
2013-09-01 | GSE46743 | GEO
Project description:During their lifespan, plants continuously respond to a multitude of stressful factors that affects their development and reproductive fitness through a sophisticated variety of physiological, biochemical, transcriptional, and epigenetic mechanisms. Dynamic changes in chromatin structure and concomitant transcriptional variations play an important role in both stress response and adaptation. Epigenetic memory mechanisms seem to be involved because chromatin and expression patterns can be indeed stably maintained during cell division, once the triggering stimulus has been removed. In this study we performed transcriptome and genome-wide analysis of histone modifications of maize plants subjected to a mild and prolonged drought stress followed by a complete recovery phase. Results led to the identification of stress-responsive genes in which variations in transcript and/or histone modification levels persist after stress removal. Genes not showing an immediate response to stress, but perceiving and storing stress signal for a delayed response were also identified. This provides valuable information about genes and mechanisms utilized by plants to adapt to stressful environment and potentially involved in stress memory. We also report that drought stress alters flowering and inflorescences patterning, possibly by affecting expression and chromatin of flowering regulatory genes.
2019-10-02 | GSE128002 | GEO
Project description:While exposure to adverse life events and subsequent dysregulation of the stress hormone response broadly confer risk for depression, the specific molecular mechanisms mediating this risk are poorly understood. Through pharmacologic activation of the stress hormone response in blood cells we demonstrate that common genetic variants in long-range enhancer elements moderate the immediate transcriptome response to stress, and that these genetic differences are associated with increased risk for depression in the context of early adversity. Using imaging genetics we then link these common risk variants with dysregulated amygdala reactivity, an important trigger of the stress hormone response. The transcripts regulated by these risk variants in peripheral blood were also responsive to stress and stress hormone receptor activation in murine brain. Network modeling approaches suggest that these differences in transcriptional activation may mediate stress-related risk for depression by altering a functional gene network related to proteasome degradation and synaptic plasticity. A Dexamethasone Suppression Test was performed in 160 male subjects. Baseline and stimulated (3 hours after 1.5 mg dexamethasone p.o.) whole blood samples were analyzed using Illumina Human HT-12 v3 arrays.
2013-09-01 | E-GEOD-46743 | biostudies-arrayexpress
Project description:Hog1 bypasses stress-mediated downregulation of transcription by PolII redistribution and chromatin remodeling Keyword: genetic modification
2012-10-30 | GSE41451 | GEO
Project description:Despite depression being one of the most prevalent and debilitating disorders worldwide, it has been difficult to understand its pathophysiology and to develop more effective treatments. Maladaptive transcriptional regulation within limbic neural circuits, including reward processing regions such as the nucleus accumbens (NAc), in response to chronic stress is thought to be a major contributor to the development of the syndrome. Epigenetic events?in particular, histone writers and erasers?that alter chromatin structure to regulate programs of gene expression have increasingly been associated with depression-related behavioral abnormalities in animal models and in depressed humans examined postmortem. However, very little is known about the ATP-dependent chromatin remodelers that control nucleosome positioning and the packing state of chromatin. Here we show that the ACF complex, part of the ISWI family of chromatin remodelers, is persistently and selectively upregulated in the NAc of mice that are susceptible to chronic social stress, as well as in the NAc of depressed human. We further establish that ACF induction is both necessary and sufficient for susceptibility to stress-induced depressive-like behaviors. Using ChIP-seq, we demonstrate that altered ACF binding after chronic stress is strongly correlated with altered nucleosome positioning, in particular, around the transcriptional start sites of affected genes. These alterations in ACF binding and nucleosome repositioning are associated with repressed expression of a subset of genes in animals that are susceptible to chronic stress. Together, these findings establish that active ATP-dependent chromatin remodeling by the ACF complex is a key regulator in the repression of genes that mediate susceptibility to social stress, and provide novel candidate targets for improved therapeutics of depression and other stress-related disorders. c57bl/6 mice underwent chronic social defeat stress (CSDS), and social interaction test was used to separate animals into control, susceptible and resilient groups. Nucleus accumbens (NAc) tissue was collected 48 hours after the last defeat session, and then Acf1, SNF2H ChIP-seq or H3 MNase-seq were performed based on the control, susceptible, and resilient groups. Three sequencing replicates were performed on each group.
2015-09-21 | E-GEOD-54263 | biostudies-arrayexpress
Project description:Fear extinction is an adaptive behavioral process critical for organism’s survival, but deficiency in extinction may lead to PTSD. While the amygdala and its neural circuits are critical for fear extinction, the molecular identity and organizational logic of cell types that lie at the core of these circuits remain unclear. Here we report that mice deficient for amygdala-enriched gastrin-releasing peptide gene (Grp-/-) exhibit enhanced neuronal activity in the basolateral amygdala (BLA) and stronger fear conditioning, as well as deficient extinction in stress-enhanced fear learning (SEFL). rAAV2-retro-based tracing combined with visualization of the GFP knocked in the Grp gene showed that BLA receives several GRPergic conditioned stimulus projections: from the indirect auditory thalamus-to-auditory cortex pathway, medial prefrontal cortex, ventral hippocampus and ventral tegmental area. Transcription of dopamine-related genes was decreased in BLA of Grp-/- mice following SEFL extinction recall, suggesting that the GRP may mediate fear extinction regulation by dopamine.
2021-12-01 | GSE164226 | GEO