A role for the RNA Polymerase II-CTD phosphatase, FCP1 in the oxidative stress response
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE128936 | GEO | 2019/09/10
REPOSITORIES: GEO
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Project description:Skn7 is a conserved fungal heat shock factor-type transcriptional regulator. It participates in maintaining cell wall integrity and regulates the osmotic/oxidative stress response (OSR) in S. cerevisiae, where it is part of a two-component signal transduction system. Here, we comprehensively address the function of Skn7 in the human fungal pathogen Candida albicans. We provide evidence reinforcing functional divergence, with loss of the cell wall/osmotic stress-protective roles and acquisition of the ability to regulate morphogenesis on solid medium. Mapping of the Skn7 transcriptional circuitry, through combination of genome-wide expression and location technologies, pointed to a dual regulatory role encompassing OSR and filamentous growth. Genetic interaction analyses revealed close functional interactions between Skn7 and master regulators of morphogenesis, including Efg1, Cph1 and Ume6. Intracellular biochemical assays revealed that Skn7 is crucial for limiting the accumulation of reactive oxygen species (ROS) during filamentous growth on solid medium. Interestingly, functional domain mapping using site-directed mutagenesis allowed decoupling of Skn7 function in morphogenesis from protection against intracellular ROS. Our work identifies Skn7 as an integral part of the transcriptional circuitry controlling C. albicans filamentous growth and illuminates how C. albicans relies on an evolutionarily-conserved regulator to protect itself from intracellular ROS during morphological development.
2017-06-30 | GSE85276 | GEO
Project description:Skn7 is a conserved fungal heat shock factor-type transcriptional regulator. It participates in maintaining cell wall integrity and regulates the osmotic/oxidative stress response (OSR) in S. cerevisiae, where it is part of a two-component signal transduction system. Here, we comprehensively address the function of Skn7 in the human fungal pathogen Candida albicans. We provide evidence reinforcing functional divergence, with loss of the cell wall/osmotic stress-protective roles and acquisition of the ability to regulate morphogenesis on solid medium. Mapping of the Skn7 transcriptional circuitry, through combination of genome-wide expression and location technologies, pointed to a dual regulatory role encompassing OSR and filamentous growth. Genetic interaction analyses revealed close functional interactions between Skn7 and master regulators of morphogenesis, including Efg1, Cph1 and Ume6. Intracellular biochemical assays revealed that Skn7 is crucial for limiting the accumulation of reactive oxygen species (ROS) during filamentous growth on solid medium. Interestingly, functional domain mapping using site-directed mutagenesis allowed decoupling of Skn7 function in morphogenesis from protection against intracellular ROS. Our work identifies Skn7 as an integral part of the transcriptional circuitry controlling C. albicans filamentous growth and illuminates how C. albicans relies on an evolutionarily-conserved regulator to protect itself from intracellular ROS during morphological development.
2017-06-30 | GSE85275 | GEO
Project description:CDK8 is a key subunit of Mediator complex, a large multiprotein complex that is a fundamental part of the conserved eukaryotic transcriptional machinery. However, the biological functions of CDK8 in plant abiotic stress responses remain largely unexplored. Here, we demonstrated CDK8 as a critical regulator in the abscisic acid (ABA) signaling and drought response pathways in Arabidopsis. Compared to wild-type, cdk8 mutants showed reduced sensitivity to ABA, impaired stomatal apertures and hypersensitivity to drought stress. Transcriptomic and chromatin immunoprecipitation analysis revealed that CDK8 positively regulates the transcription of several ABA-responsive genes, probably through promoting the recruitment of RNA polymerase II to their promoters. We discovered that both CDK8 and SnRK2.6 interact physically with an ERF/AP2 transcription factor RAP2.6, which can directly bind to the promoters of RD29A and COLD-REGULATED 15A (COR15A) with GCC or DRE elements, thereby promoting their expression. Importantly, we also showed that CDK8 is essential for the ABA-induced expression of RAP2.6 and RAP2.6-mediated upregulation of ABA-responsive genes, indicating that CDK8 could link the SnRK2.6-mediated ABA signaling to RNA polymerase II to promote immediate transcriptional response to ABA and drought signals. Overall, our data provide new insights into the roles of CDK8 in modulating ABA signaling and drought responses.
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Project description:Changes in the transcriptome of Isc1p deficient mutants. The inositolphosphosphingolipid phospholipase C (Isc1p) of Saccharomyces cerevisiae belongs to the family of neutral sphingomyelinases that generates the bioactive sphingolipid ceramide. In this work the role of Isc1p in oxidative stress resistance and chronological lifespan was investigated. Loss of Isc1p resulted in a higher sensitivity to hydrogen peroxide that was associated with an increase in oxidative stress markers, namely intracellular oxidation, protein carbonylation and lipid peroxidation. Microarray analysis showed that Isc1p deficiency upregulated the iron regulon leading to increased levels of iron, which is known to catalyze the production of the highly reactive hydroxyl radicals via the Fenton reaction. In agreement, iron chelation suppressed hydrogen peroxide sensitivity of isc1D mutants. Cells lacking Isc1p also displayed a shortened chronological lifespan associated with oxidative stress markers and ageing of parental cells was correlated with a decrease in Isc1p activity. The analysis of DNA fragmentation and caspase activity showed that Isc1p deficiency increased apoptotic programmed cell death associated with oxidative stress and ageing. Furthermore, deletion of Yca1p metacaspase suppressed the oxidative stress sensitivity and premature ageing phenotypes of isc1D mutants. These results indicate that Isc1p plays an important role in the regulation of cellular redox homeostasis, through modulation of iron levels, and of apoptosis.
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Project description:The C-terminal domain (CTD) of RNA polymerase II (RNAPII) is composed of heptapeptide repeats, which play a key regulatory role in gene expression. Using genetic interaction and mRNA expression analysis we found that truncating the CTD resulted in distinct changes to cellular function. Truncating the CTD altered RNAPII occupancy to not only cause decreases, but also increases in mRNA levels. The latter were largely mediated by promoter elements, and in part were linked to the transcription factor Rpn4. The mediator subunit Cdk8 was enriched at promoters of these genes, and its removal not only restored normal mRNA and RNAPII occupancy levels, but also reduced the abnormally high cellular amounts of Rpn4. This suggested a positive role of Cdk8 in relationship to RNAPII, which contrasted with the negative role at the activated INO1 gene. Here, loss of CDK8 suppressed the reduced mRNA expression and RNAPII occupancy levels of CTD truncation mutants.
2013-09-13 | GSE43120 | GEO
Project description:Martinez-Guimera2017 - Generic redox signalling model without negative regulation (Model 1)
This model is described in the article:
'Molecular habituation' as a
potential mechanism of gradual homeostatic loss with age.
Martinez Guimera A, Welsh CM,
Proctor CJ, McArdle A, Shanley DP.
Mech. Ageing Dev. 2017 Nov; :
Abstract:
The ability of reactive oxygen species (ROS) to cause
molecular damage has meant that chronic oxidative stress has
been mostly studied from the point of view of being a source of
toxicity to the cell. However, the known duality of ROS
molecules as both damaging agents and cellular redox signals
implies another perspective in the study of sustained oxidative
stress. This is a perspective of studying oxidative stress as a
constitutive signal within the cell. In this work, we adopt a
theoretical perspective as an exploratory and explanatory
approach to examine how chronic oxidative stress can interfere
with signal processing by redox signalling pathways in the
cell. We report that constitutive signals can give rise to a
'molecular habituation' effect that can prime for a gradual
loss of biological function. This is because a constitutive
signal in the environment has the potential to reduce the
responsiveness of a signalling pathway through the prolonged
activation of negative regulators. Additionally, we demonstrate
how this phenomenon is likely to occur in different signalling
pathways exposed to persistent signals and furthermore at
different levels of biological organisation.
This model is hosted on
BioModels Database
and identified by:
MODEL1710260000.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
| MODEL1710260000 | BioModels
Project description:Martinez-Guimera2017 - Generic redox signalling model with negative feedback regulation (Model 2)
This model is described in the article:
'Molecular habituation' as a
potential mechanism of gradual homeostatic loss with age.
Martinez Guimera A, Welsh CM,
Proctor CJ, McArdle A, Shanley DP.
Mech. Ageing Dev. 2017 Nov; :
Abstract:
The ability of reactive oxygen species (ROS) to cause
molecular damage has meant that chronic oxidative stress has
been mostly studied from the point of view of being a source of
toxicity to the cell. However, the known duality of ROS
molecules as both damaging agents and cellular redox signals
implies another perspective in the study of sustained oxidative
stress. This is a perspective of studying oxidative stress as a
constitutive signal within the cell. In this work, we adopt a
theoretical perspective as an exploratory and explanatory
approach to examine how chronic oxidative stress can interfere
with signal processing by redox signalling pathways in the
cell. We report that constitutive signals can give rise to a
'molecular habituation' effect that can prime for a gradual
loss of biological function. This is because a constitutive
signal in the environment has the potential to reduce the
responsiveness of a signalling pathway through the prolonged
activation of negative regulators. Additionally, we demonstrate
how this phenomenon is likely to occur in different signalling
pathways exposed to persistent signals and furthermore at
different levels of biological organisation.
This model is hosted on
BioModels Database
and identified by:
MODEL1710260001.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
| MODEL1710260001 | BioModels
Project description:Martinez-Guimera2017 - Generic redox signalling model with negative feedforward regulation (Model 3)
This model is described in the article:
'Molecular habituation' as a
potential mechanism of gradual homeostatic loss with age.
Martinez Guimera A, Welsh CM,
Proctor CJ, McArdle A, Shanley DP.
Mech. Ageing Dev. 2017 Nov; :
Abstract:
The ability of reactive oxygen species (ROS) to cause
molecular damage has meant that chronic oxidative stress has
been mostly studied from the point of view of being a source of
toxicity to the cell. However, the known duality of ROS
molecules as both damaging agents and cellular redox signals
implies another perspective in the study of sustained oxidative
stress. This is a perspective of studying oxidative stress as a
constitutive signal within the cell. In this work, we adopt a
theoretical perspective as an exploratory and explanatory
approach to examine how chronic oxidative stress can interfere
with signal processing by redox signalling pathways in the
cell. We report that constitutive signals can give rise to a
'molecular habituation' effect that can prime for a gradual
loss of biological function. This is because a constitutive
signal in the environment has the potential to reduce the
responsiveness of a signalling pathway through the prolonged
activation of negative regulators. Additionally, we demonstrate
how this phenomenon is likely to occur in different signalling
pathways exposed to persistent signals and furthermore at
different levels of biological organisation.
This model is hosted on
BioModels Database
and identified by:
MODEL1710260002.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
| MODEL1710260002 | BioModels
Project description:Martinez-Guimera2017 - Generic negative feedback circuit (Model 4)
This model is described in the article:
'Molecular habituation' as a
potential mechanism of gradual homeostatic loss with age.
Martinez Guimera A, Welsh CM,
Proctor CJ, McArdle A, Shanley DP.
Mech. Ageing Dev. 2017 Nov; :
Abstract:
The ability of reactive oxygen species (ROS) to cause
molecular damage has meant that chronic oxidative stress has
been mostly studied from the point of view of being a source of
toxicity to the cell. However, the known duality of ROS
molecules as both damaging agents and cellular redox signals
implies another perspective in the study of sustained oxidative
stress. This is a perspective of studying oxidative stress as a
constitutive signal within the cell. In this work, we adopt a
theoretical perspective as an exploratory and explanatory
approach to examine how chronic oxidative stress can interfere
with signal processing by redox signalling pathways in the
cell. We report that constitutive signals can give rise to a
'molecular habituation' effect that can prime for a gradual
loss of biological function. This is because a constitutive
signal in the environment has the potential to reduce the
responsiveness of a signalling pathway through the prolonged
activation of negative regulators. Additionally, we demonstrate
how this phenomenon is likely to occur in different signalling
pathways exposed to persistent signals and furthermore at
different levels of biological organisation.
This model is hosted on
BioModels Database
and identified by:
MODEL1710260003.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
| MODEL1710260003 | BioModels
Project description:Martinez-Guimera2017 - Generic negative feedforward circuit (Model 5)
This model is described in the article:
'Molecular habituation' as a
potential mechanism of gradual homeostatic loss with age.
Martinez Guimera A, Welsh CM,
Proctor CJ, McArdle A, Shanley DP.
Mech. Ageing Dev. 2017 Nov; :
Abstract:
The ability of reactive oxygen species (ROS) to cause
molecular damage has meant that chronic oxidative stress has
been mostly studied from the point of view of being a source of
toxicity to the cell. However, the known duality of ROS
molecules as both damaging agents and cellular redox signals
implies another perspective in the study of sustained oxidative
stress. This is a perspective of studying oxidative stress as a
constitutive signal within the cell. In this work, we adopt a
theoretical perspective as an exploratory and explanatory
approach to examine how chronic oxidative stress can interfere
with signal processing by redox signalling pathways in the
cell. We report that constitutive signals can give rise to a
'molecular habituation' effect that can prime for a gradual
loss of biological function. This is because a constitutive
signal in the environment has the potential to reduce the
responsiveness of a signalling pathway through the prolonged
activation of negative regulators. Additionally, we demonstrate
how this phenomenon is likely to occur in different signalling
pathways exposed to persistent signals and furthermore at
different levels of biological organisation.
This model is hosted on
BioModels Database
and identified by:
MODEL1710260004.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
| MODEL1710260004 | BioModels