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    Stochastic pulse regulation in bacterial stress response (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-10-08
    Description: Gene regulatory circuits can use dynamic, and even stochastic, strategies to respond to environmental conditions. We examined activation of the general stress response mediated by the alternative sigma factor, sigma(B), in individual Bacillus subtilis cells. We observed that energy stress activates sigma(B) in discrete stochastic pulses, with increasing levels of stress leading to higher pulse frequencies. By perturbing and rewiring the endogenous system, we found that this behavior results from three key features of the sigma(B) circuit: an ultrasensitive phosphorylation switch; stochasticity ("noise"), which activates that switch; and a mixed (positive and negative) transcriptional feedback, which can both amplify a pulse and switch it off. Together, these results show how prokaryotes encode signals using stochastic pulse frequency modulation through a compact regulatory architecture.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100694/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100694/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Locke, James C W -- Young, Jonathan W -- Fontes, Michelle -- Hernandez Jimenez, Maria Jesus -- Elowitz, Michael B -- P50 GM068763/GM/NIGMS NIH HHS/ -- R01 GM079771/GM/NIGMS NIH HHS/ -- R01GM079771/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Oct 21;334(6054):366-9. doi: 10.1126/science.1208144. Epub 2011 Oct 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Division of Biology and Bioengineering, Broad Center, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21979936" target="_blank"〉PubMed〈/a〉
    Keywords: Bacillus subtilis/*genetics/metabolism/*physiology ; Bacterial Proteins/genetics/*metabolism ; Carrier Proteins/genetics/metabolism ; Feedback, Physiological ; Gene Expression Regulation, Bacterial ; *Gene Regulatory Networks ; Mycophenolic Acid/pharmacology ; Phosphoric Monoester Hydrolases/genetics/metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics/metabolism ; Sigma Factor/genetics/*metabolism ; Stochastic Processes ; *Stress, Physiological ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Gene regulation at the single-cell level (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-03-26
    Description: The quantitative relation between transcription factor concentrations and the rate of protein production from downstream genes is central to the function of genetic networks. Here we show that this relation, which we call the gene regulation function (GRF), fluctuates dynamically in individual living cells, thereby limiting the accuracy with which transcriptional genetic circuits can transfer signals. Using fluorescent reporter genes and fusion proteins, we characterized the bacteriophage lambda promoter P(R) in Escherichia coli. A novel technique based on binomial errors in protein partitioning enabled calibration of in vivo biochemical parameters in molecular units. We found that protein production rates fluctuate over a time scale of about one cell cycle, while intrinsic noise decays rapidly. Thus, biochemical parameters, noise, and slowly varying cellular states together determine the effective single-cell GRF. These results can form a basis for quantitative modeling of natural gene circuits and for design of synthetic ones.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosenfeld, Nitzan -- Young, Jonathan W -- Alon, Uri -- Swain, Peter S -- Elowitz, Michael B -- New York, N.Y. -- Science. 2005 Mar 25;307(5717):1962-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Molecular Cell Biology and Physics of Complex Systems, Weizmann Institute of Science, Rehovot, 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15790856" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/biosynthesis ; Bacteriophage lambda/genetics ; Cell Cycle ; DNA-Binding Proteins/*metabolism ; Escherichia coli/*genetics/growth & development/metabolism ; Escherichia coli Proteins/biosynthesis/*metabolism ; Fluorescence ; *Gene Expression Regulation, Bacterial ; Green Fluorescent Proteins/biosynthesis ; Image Processing, Computer-Assisted ; Luminescent Proteins/biosynthesis ; Mathematics ; Microscopy, Fluorescence ; *Models, Genetic ; Promoter Regions, Genetic ; Recombinant Fusion Proteins/metabolism ; Repressor Proteins/*metabolism ; Signal Transduction ; Transcription Factors/*metabolism ; Transcription, Genetic ; Viral Proteins ; Viral Regulatory and Accessory Proteins
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
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    PAPER CURRENT
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