Systematic Identification of Signal-Activated Stochastic Gene Regulation
Gregor Neuert,Gregor Neuert,Brian Munsky,Rui Zhen Tan,Rui Zhen Tan,Rui Zhen Tan,Leonid Teytelman,Mustafa Khammash,Mustafa Khammash,Alexander van Oudenaarden,Alexander van Oudenaarden +10 more
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TLDR
An integrated experimental and computational procedure to capture, predict, and understand the temporal dynamics of signal-activated gene regulation at single-molecule and single-cell resolution and correctly predicts the transcriptional dynamics of cells in response to different environmental and genetic perturbations.Abstract:
Although much has been done to elucidate the biochemistry of signal transduction and gene regulatory pathways, it remains difficult to understand or predict quantitative responses. We integrate single-cell experiments with stochastic analyses, to identify predictive models of transcriptional dynamics for the osmotic stress response pathway in Saccharomyces cerevisiae. We generate models with varying complexity and use parameter estimation and cross-validation analyses to select the most predictive model. This model yields insight into several dynamical features, including multistep regulation and switchlike activation for several osmosensitive genes. Furthermore, the model correctly predicts the transcriptional dynamics of cells in response to different environmental and genetic perturbations. Because our approach is general, it should facilitate a predictive understanding for signal-activated transcription of other genes in other pathways or organisms.read more
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疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
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References
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疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Journal ArticleDOI
Stochastic mRNA Synthesis in Mammalian Cells
TL;DR: The results demonstrate that gene expression in mammalian cells is subject to large, intrinsically random fluctuations and raise questions about how cells are able to function in the face of such noise.
Journal ArticleDOI
Osmotic Stress Signaling and Osmoadaptation in Yeasts
TL;DR: An integrated understanding of osmoadaptation requires not only knowledge of the function of many uncharacterized genes but also further insight into the time line of events, their interdependence, their dynamics, and their spatial organization as well as the importance of subtle effects.
PatentDOI
IMAGING INDIVIDUAL mRNA MOLECULES USING MULTIPLE SINGLY LABELED PROBES
Arjun Raj,Sanjay Tyagi +1 more
TL;DR: In this article, a method for probing a target sequence of messenger ribonucleic acid molecules (mRNA's) in a fixed, permeabilized cell, including at least 30 non- overlapping probe binding regions of 15-100 nucleotides, was proposed.
Journal ArticleDOI
Control of Stochasticity in Eukaryotic Gene Expression
Jonathan M. Raser,Erin K. O'Shea +1 more
TL;DR: A model in which the balance between promoter activation and transcription influences the variability in messenger RNA levels is proposed, which suggests that noise is an evolvable trait that can be optimized to balance fidelity and diversity in eukaryotic gene expression.
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