Deciphering Dynamic Dose Responses of Natural Promoters and Single <i>cis</i> Elements upon Osmotic and Oxidative Stress in Yeast

Dolz‐Edo, Laura; Rienzo, Alessandro; Poveda-Huertes, Daniel; Pascual-Ahuir, Amparo; Proft, Markus

doi:10.1128/mcb.00240-13

Cited by 28 publications

(36 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is important to note that the sensitivity of gene expression to a common signal, such as a nutrient or a stress, can be different for specific responsive genes. Here, the chromatin structure and the combination of different cis-regulatory elements in promoters have been implicated in creating characteristic dose sensitivities of yeast genes (14,15). In our present study, we reveal different strategies that ensure an appropriate transcriptional activation corresponding to subtle environmental changes.…”

Section: Discussionmentioning

confidence: 88%

“…It is largely unknown how gene regulatory systems adapt to these "suboptimal" signals, mostly because it is experimentally challenging to quantify the dynamic gene expression upon gradually changing stimulation. Here, the recent application of destabilized luciferase reporters for continuous live-cell measurements in yeast turned out to be especially useful (15,38). This real-time survey of gene expression activity reveals the dynamic range of differentially regulated groups of genes.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, among the often numerous genes activated in response to a given stress, the cell has to impose different sensitivities to guarantee an equilibrated adaptive response. Here, chromatin structure has been implied in modulating the threshold of gene activation in the yeast phosphate response (14), and different natural promoters and cis regulatory elements confer characteristic dose-sensitive expression profiles upon osmotic and oxidative stress (15).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Different Mechanisms Confer Gradual Control and Memory at Nutrient- and Stress-Regulated Genes in Yeast

Rienzo

Poveda-Huertes

Aydin

et al. 2015

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

c Cells respond to environmental stimuli by fine-tuned regulation of gene expression. Here we investigated the dose-dependent modulation of gene expression at high temporal resolution in response to nutrient and stress signals in yeast. The GAL1 activity in cell populations is modulated in a well-defined range of galactose concentrations, correlating with a dynamic change of histone remodeling and RNA polymerase II (RNAPII) association. This behavior is the result of a heterogeneous induction delay caused by decreasing inducer concentrations across the population. Chromatin remodeling appears to be the basis for the dynamic GAL1 expression, because mutants with impaired histone dynamics show severely truncated dose-response profiles. In contrast, the GRE2 promoter operates like a rapid off/on switch in response to increasing osmotic stress, with almost constant expression rates and exclusively temporal regulation of histone remodeling and RNAPII occupancy. The Gal3 inducer and the Hog1 mitogen-activated protein (MAP) kinase seem to determine the different dose-response strategies at the two promoters. Accordingly, GAL1 becomes highly sensitive and dose independent if previously stimulated because of residual Gal3 levels, whereas GRE2 expression diminishes upon repeated stimulation due to acquired stress resistance. Our analysis reveals important differences in the way dynamic signals create dose-sensitive gene expression outputs.C ells continuously adapt their protein composition to changing environmental conditions. The regulation of gene expression is one of the fundamental mechanisms to adjust the global protein repertoire of the cell in order to maintain cell function and integrity in response to environmental challenges. Budding yeast is a powerful model to unravel the modes of transcriptional adaptation at the levels both of specific genes and of the whole organism (1, 2). Additionally, the basic structure of the signaling cascades responding to environmental perturbations is conserved from yeast to humans. It implies the alteration of core kinase activities, which modulate the expression of defense genes through a range of specific transcription factors. Extensive knowledge which precisely describes the molecular machinery and its global impact on gene expression in response to many types of stress has accumulated (3-7). However, the vast majority of these studies are performed with harsh environmental insults and therefore saturating stimulation. As a consequence, only very limited information or approaches are available to understand how cells adapt their gene expression programs to small or gradual changes in their environment.It is assumed that cells have acquired mechanisms that ensure a transcriptional response which is finely adjusted according to the strength of the stress or stimulation. However, the nature of the signaling molecules which confer gradual transcription outputs remains to be determined in most cases. Fine-tuning of gene expression responses can occur with different purposes, and th...

show abstract

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Different Mechanisms Confer Gradual Control and Memory at Nutrient- and Stress-Regulated Genes in Yeast

Rienzo

Poveda-Huertes

Aydin

et al. 2015

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The TonE/ORE enhancer is also present in other mammalian genes that promote the accumulation of compatible organic osmolytes, including AR (33). Furthermore, salinity-responsive CREs have been identified in yeast (70) and in the quinoa plant 1 and MIPS genes that match a common consensus, which has OSRE activity. The CRE fitting this consensus motif was named OSRE1.…”

Section: Discussionmentioning

confidence: 99%

Osmolality/salinity-responsive enhancers (OSREs) control induction of osmoprotective genes in euryhaline fish

Wang

Kültz

2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Fish respond to salinity stress by transcriptional induction of many genes, but the mechanism of their osmotic regulation is unknown. We developed a reporter assay using cells derived from the brain of the tilapia Oreochromis mossambicus (OmB cells) to identify osmolality/salinity-responsive enhancers (OSREs) in the genes of O. mossambicus. Genomic DNA comprising the regulatory regions of two strongly salinity-induced genes, inositol monophosphatase 1 (IMPA1.1) and myo-inositol phosphate synthase (MIPS), was isolated and analyzed with dual luciferase enhancer trap reporter assays. We identified five sequences (two in IMPA1.1 and three in MIPS) that share a common consensus element (DDKGGAAWWDWWYDNRB), which we named "OSRE1." Additional OSREs that were less effective in conferring salinity-induced trans-activation and do not match the OSRE1 consensus also were identified in both MIPS and IMPA1.1. Although OSRE1 shares homology with the mammalian osmotic-response element/tonicity-responsive enhancer (ORE/TonE) enhancer, the latter is insufficient to confer osmotic induction in fish. Like other enhancers, OSRE1 trans-activates genes independent of orientation. We conclude that OSRE1 is a cis-regulatory element (CRE) that enhances the hyperosmotic induction of osmoregulated genes in fish. Our study also shows that tailored reporter assays developed for OmB cells facilitate the identification of CREs in fish genomes. Knowledge of the OSRE1 motif allows affinity-purification of the corresponding transcription factor and computational approaches for enhancer screening of fish genomes. Moreover, our study enables targeted inactivation of OSRE1 enhancers, a method superior to gene knockout for functional characterization because it confines impairment of gene function to a specific context (salinity stress) and eliminates pitfalls of constitutive gene knockouts (embryonic lethality, developmental compensation). biochemical evolution | compatible osmolytes | osmotic stress signaling | enhancer | CRE

show abstract

“…Perturbations of the transcriptional response by changes in the cells physiology are not restricted to osmotic stress. It has been recently shown that also oxidative stress, at threshold levels, interferes with efficient transcriptional activation and, more importantly, that mutants in reactive oxygen species detoxification systems show much less dynamic transcriptional responses (28). Thus, the dynamic of a gene expression response to stress is to a great part dependent on cell physiology.…”

mentioning

confidence: 99%

Coordinated Gene Regulation in the Initial Phase of Salt Stress Adaptation

Vanacloig-Pedros

Bets-Plasencia

Pascual-Ahuir

et al. 2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Deciphering Dynamic Dose Responses of Natural Promoters and Single cis Elements upon Osmotic and Oxidative Stress in Yeast

Cited by 28 publications

References 55 publications

Different Mechanisms Confer Gradual Control and Memory at Nutrient- and Stress-Regulated Genes in Yeast

Different Mechanisms Confer Gradual Control and Memory at Nutrient- and Stress-Regulated Genes in Yeast

Osmolality/salinity-responsive enhancers (OSREs) control induction of osmoprotective genes in euryhaline fish

Coordinated Gene Regulation in the Initial Phase of Salt Stress Adaptation

Contact Info

Product

Resources

About