scholarly journals Stochastic modelling of nucleocytoplasmic oscillations of the transcription factor Msn2 in yeast

2008 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Didier Gonze ◽  
Michel Jacquet ◽  
Albert Goldbeter

Stress induces oscillatory nucleocytoplasmic shuttling of the transcription factor Msn2 in yeast. The subcellular localization of Msn2 is controlled by the cAMP-dependent protein kinase, PKA. Recent experimental observations corroborated by a deterministic computational model for the cAMP–PKA pathway in yeast suggest that the oscillatory dynamics of Msn2 results from the periodic activation of PKA associated with stress-induced oscillations in the level of cAMP. The model accounts for the occurrence of oscillations of Msn2 in a window bounded by two critical values of the stress intensity. In contrast to the rather irregular oscillatory behaviour observed within single yeast cells by means of fluorescence measurements, the deterministic model can only produce a regular pattern of oscillations. To investigate whether the experimentally observed variability could be explained by molecular noise due to the small number of molecules involved in the oscillatory mechanism, we examine a stochastic version of the model for periodic nucleocytoplasmic shuttling of Msn2 coupled to oscillations in the cAMP–PKA pathway. The results of stochastic simulations compare well to the irregular oscillations observed experimentally in the nucleocytoplasmic shuttling of Msn2 in individual yeast cells. The stochastic model retains the property of oscillations within a range bounded by two critical values of stress intensity. We determine the dynamic behaviour as a function of this control parameter and show that the effect of noise markedly depends on the distance from the bifurcation points in the domain of oscillatory behaviour. Finally, we assess the role played by thresholds due to zero-order ultrasensitivity in phosphorylation–dephosphorylation cycles, both in the cAMP–PKA pathway and in the reactions controlling nucleocytoplasmic shuttling of Msn2. In regard to these thresholds, stochastic simulations show that large-amplitude variations of Msn2 associated with large-amplitude oscillations in cAMP can occur outside the domain of sustained oscillations predicted by the deterministic approach.

Genetics ◽  
1999 ◽  
Vol 153 (4) ◽  
pp. 1573-1581 ◽  
Author(s):  
Susanna Chou ◽  
Sukalyan Chatterjee ◽  
Mark Lee ◽  
Kevin Struhl

Abstract The general transcription factor IIA (TFIIA) forms a complex with TFIID at the TATA promoter element, and it inhibits the function of several negative regulators of the TATA-binding protein (TBP) subunit of TFIID. Biochemical experiments suggest that TFIIA is important in the response to transcriptional activators because activation domains can interact with TFIIA, increase recruitment of TFIID and TFIIA to the promoter, and promote isomerization of the TFIID-TFIIA-TATA complex. Here, we describe a double-shut-off approach to deplete yeast cells of Toa1, the large subunit of TFIIA, to <1% of the wild-type level. Interestingly, such TFIIA-depleted cells are essentially unaffected for activation by heat shock factor, Ace1, and Gal4-VP16. However, depletion of TFIIA causes a general two- to threefold decrease of transcription from most yeast promoters and a specific cell-cycle arrest at the G2-M boundary. These results indicate that transcriptional activation in vivo can occur in the absence of TFIIA.


2020 ◽  
Vol 21 (6) ◽  
pp. 2177 ◽  
Author(s):  
Bo Li ◽  
Jia-Cheng Zheng ◽  
Ting-Ting Wang ◽  
Dong-Hong Min ◽  
Wen-Liang Wei ◽  
...  

Vascular plant one-zinc-finger (VOZ) transcription factor, a plant specific one-zinc-finger-type transcriptional activator, is involved in regulating numerous biological processes such as floral induction and development, defense against pathogens, and response to multiple types of abiotic stress. Six VOZ transcription factor-encoding genes (GmVOZs) have been reported to exist in the soybean (Glycine max) genome. In spite of this, little information is currently available regarding GmVOZs. In this study, GmVOZs were cloned and characterized. GmVOZ genes encode proteins possessing transcriptional activation activity in yeast cells. GmVOZ1E, GmVOZ2B, and GmVOZ2D gene products were widely dispersed in the cytosol, while GmVOZ1G was primarily located in the nucleus. GmVOZs displayed a differential expression profile under dehydration, salt, and salicylic acid (SA) stress conditions. Among them, GmVOZ1G showed a significantly induced expression in response to all stress treatments. Overexpression of GmVOZ1G in soybean hairy roots resulted in a greater tolerance to drought and salt stress. In contrast, RNA interference (RNAi) soybean hairy roots suppressing GmVOZ1G were more sensitive to both of these stresses. Under drought treatment, soybean composite plants with an overexpression of hairy roots had higher relative water content (RWC). In response to drought and salt stress, lower malondialdehyde (MDA) accumulation and higher peroxidase (POD) and superoxide dismutase (SOD) activities were observed in soybean composite seedlings with an overexpression of hairy roots. The opposite results for each physiological parameter were obtained in RNAi lines. In conclusion, GmVOZ1G positively regulates drought and salt stress tolerance in soybean hairy roots. Our results will be valuable for the functional characterization of soybean VOZ transcription factors under abiotic stress.


1990 ◽  
Vol 10 (7) ◽  
pp. 3415-3420
Author(s):  
M W Van Dyke ◽  
M Sawadogo

The existence of separable functions within the human class II general transcription factor TFIID was probed for differential sensitivity to mild proteolytic treatment. Independent of whether TFIID was bound to DNA or free in solution, partial digestion with either one of a variety of nonspecific endoproteases generated a protease-resistant protein product that retained specific DNA recognition, as revealed by DNase I footprinting. However, in contrast to native TFIID, which interacts with the adenovirus major late (ML) promoter over a very broad DNA region, partially proteolyzed TFIID interacted with only a small region of the ML promoter immediately surrounding the TATA sequence. This novel footprint was very similar to that observed with the TATA factor purified from yeast cells. Partially proteolyzed human TFIID could form stable complexes that were resistant to challenge by exogenous templates. It could also nucleate the assembly of transcription complexes on the ML promoter with an efficiency comparable to that of native TFIID, yielding similar levels of transcription initiation. These results suggest a model in which the human TFIID protein is composed of at least two different regions or polypeptides: a protease-resistant "core," which by itself is sufficient for promoter recognition and basal transcriptional levels, and a protease-sensitive "tail," which interacts with downstream promoter regions and may be involved in regulatory processes.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Diego Velázquez ◽  
Marcel Albacar ◽  
Chunyi Zhang ◽  
Carlos Calafí ◽  
María López-Malo ◽  
...  

Abstract Control of the protein phosphorylation status is a major mechanism for regulation of cellular processes, and its alteration often lead to functional disorders. Ppz1, a protein phosphatase only found in fungi, is the most toxic protein when overexpressed in Saccharomyces cerevisiae. To investigate the molecular basis of this phenomenon, we carried out combined genome-wide transcriptomic and phosphoproteomic analyses. We have found that Ppz1 overexpression causes major changes in gene expression, affecting ~ 20% of the genome, together with oxidative stress and increase in total adenylate pools. Concurrently, we observe changes in the phosphorylation pattern of near 400 proteins (mainly dephosphorylated), including many proteins involved in mitotic cell cycle and bud emergence, rapid dephosphorylation of Snf1 and its downstream transcription factor Mig1, and phosphorylation of Hog1 and its downstream transcription factor Sko1. Deletion of HOG1 attenuates the growth defect of Ppz1-overexpressing cells, while that of SKO1 aggravates it. Our results demonstrate that Ppz1 overexpression has a widespread impact in the yeast cells and reveals new aspects of the regulation of the cell cycle.


2015 ◽  
Vol 108 (2) ◽  
pp. 463a
Author(s):  
Huaqing Cai ◽  
Mariko Katoh-Kurasawa ◽  
Tetsuya Muramoto ◽  
Balaji Santhanam ◽  
Yu Long ◽  
...  

2016 ◽  
Vol 110 (3) ◽  
pp. 231a
Author(s):  
Adam Wollman ◽  
Sviatlana Shashkova ◽  
Erik Hedlund ◽  
Stefan Hohmann ◽  
Mark C. Leake

2008 ◽  
Vol 7 (6) ◽  
pp. 949-957 ◽  
Author(s):  
Masafumi Nishizawa ◽  
Tae Komai ◽  
Nobuyuki Morohashi ◽  
Mitsuhiro Shimizu ◽  
Akio Toh-e

ABSTRACT Nutrient-sensing kinases play important roles for the yeast Saccharomyces cerevisiae to adapt to new nutrient conditions when the nutrient status changes. Our previous global gene expression analysis revealed that the Pho85 kinase, one of the yeast nutrient-sensing kinases, is involved in the changes in gene expression profiles when yeast cells undergo a diauxic shift. We also found that the stationary phase-specific genes SNZ1 and SNO1, whch share a common promoter, are not properly induced when Pho85 is absent. To examine the role of the kinase in SNZ1/SNO1 regulation, we analyzed their expression during the growth of various yeast mutants, including those affecting Pho85 function or lacking the Pho4 transcription factor, an in vivo substrate of Pho85, and tested Pho4 binding by chromatin immunoprecipitation. Pho4 exhibits temporal binding to the SNZ1/SNO1 promoter to down-regulate the promoter activity, and a Δpho4 mutation advances the timing of SNZ1/SNO1 expression. SNZ2, another member of the SNZ/SNO family, is expressed at an earlier growth stage than SNZ1, and Pho4 does not affect this timing, although Pho85 is required for SNZ2 expression. Thus, Pho4 appears to regulate the different timing of the expression of the SNZ/SNO family members. Pho4 binding to the SNZ1/SNO1 promoter is accompanied by alterations in chromatin structure, and Rpd3 histone deacetylase is required for the proper timing of SNZ1/SNO1 expression, while Asf1 histone chaperone is indispensable for their expression. These results imply that Pho4 plays positive and negative roles in transcriptional regulation, with both cases involving structural changes in its target chromatin.


Science ◽  
2014 ◽  
Vol 343 (6177) ◽  
pp. 1249531-1249531 ◽  
Author(s):  
H. Cai ◽  
M. Katoh-Kurasawa ◽  
T. Muramoto ◽  
B. Santhanam ◽  
Y. Long ◽  
...  

1995 ◽  
Vol 29 (4) ◽  
pp. 711-720 ◽  
Author(s):  
Michael J. Holdsworth ◽  
Juan Mu�oz-Blanco ◽  
Michael Hammond-Kosack ◽  
Vincent Colot ◽  
Wolfgang Schuch ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245094
Author(s):  
Michael A. Rowland ◽  
Kevin R. Pilkiewicz ◽  
Michael L. Mayo

The transcriptional network determines a cell’s internal state by regulating protein expression in response to changes in the local environment. Due to the interconnected nature of this network, information encoded in the abundance of various proteins will often propagate across chains of noisy intermediate signaling events. The data-processing inequality (DPI) leads us to expect that this intracellular game of “telephone” should degrade this type of signal, with longer chains losing successively more information to noise. However, a previous modeling effort predicted that because the steps of these signaling cascades do not truly represent independent stages of data processing, the limits of the DPI could seemingly be surpassed, and the amount of transmitted information could actually increase with chain length. What that work did not examine was whether this regime of growing information transmission was attainable by a signaling system constrained by the mechanistic details of more complex protein-binding kinetics. Here we address this knowledge gap through the lens of information theory by examining a model that explicitly accounts for the binding of each transcription factor to DNA. We analyze this model by comparing stochastic simulations of the fully nonlinear kinetics to simulations constrained by the linear response approximations that displayed a regime of growing information. Our simulations show that even when molecular binding is considered, there remains a regime wherein the transmitted information can grow with cascade length, but ends after a critical number of links determined by the kinetic parameter values. This inflection point marks where correlations decay in response to an oversaturation of binding sites, screening informative transcription factor fluctuations from further propagation down the chain where they eventually become indistinguishable from the surrounding levels of noise.


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