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  • 1
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    Chromatin decouples promoter threshold from dynamic range (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-04-18
    Description: Chromatin influences gene expression by restricting access of DNA binding proteins to their cognate sites in the genome. Large-scale characterization of nucleosome positioning in Saccharomyces cerevisiae has revealed a stereotyped promoter organization in which a nucleosome-free region (NFR) is present within several hundred base pairs upstream of the translation start site. Many transcription factors bind within NFRs and nucleate chromatin remodelling events which then expose other cis-regulatory elements. However, it is not clear how transcription-factor binding and chromatin influence quantitative attributes of gene expression. Here we show that nucleosomes function largely to decouple the threshold of induction from dynamic range. With a series of variants of one promoter, we establish that the affinity of exposed binding sites is a primary determinant of the level of physiological stimulus necessary for substantial gene activation, and sites located within nucleosomal regions serve to scale expression once chromatin is remodelled. Furthermore, we find that the S. cerevisiae phosphate response (PHO) pathway exploits these promoter designs to tailor gene expression to different environmental phosphate levels. Our results suggest that the interplay of chromatin and binding-site affinity provides a mechanism for fine-tuning responses to the same cellular state. Moreover, these findings may be a starting point for more detailed models of eukaryotic transcriptional control.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2435410/" 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/PMC2435410/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lam, Felix H -- Steger, David J -- O'Shea, Erin K -- R01 GM051377/GM/NIGMS NIH HHS/ -- R01 GM051377-15/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 May 8;453(7192):246-50. doi: 10.1038/nature06867. Epub 2008 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Molecular and Cellular Biology, Faculty of Arts and Sciences Center for Systems Biology, Harvard University, 7 Divinity Avenue, Bauer 307, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18418379" target="_blank"〉PubMed〈/a〉
    Keywords: Chromatin/*genetics/*metabolism ; DNA-Binding Proteins/genetics ; *Gene Expression Regulation, Fungal ; Genes, Fungal/genetics ; Genes, Reporter/genetics ; Models, Genetic ; Nucleosomes/genetics/metabolism ; Peptide Chain Initiation, Translational ; Phosphates/pharmacology ; Promoter Regions, Genetic/*genetics ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/genetics ; Transcription Factors/genetics ; Transcriptional Activation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Biofuels. Engineering alcohol tolerance in yeast (2014)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2014-10-04
    Description: Ethanol toxicity in the yeast Saccharomyces cerevisiae limits titer and productivity in the industrial production of transportation bioethanol. We show that strengthening the opposing potassium and proton electrochemical membrane gradients is a mechanism that enhances general resistance to multiple alcohols. The elevation of extracellular potassium and pH physically bolsters these gradients, increasing tolerance to higher alcohols and ethanol fermentation in commercial and laboratory strains (including a xylose-fermenting strain) under industrial-like conditions. Production per cell remains largely unchanged, with improvements deriving from heightened population viability. Likewise, up-regulation of the potassium and proton pumps in the laboratory strain enhances performance to levels exceeding those of industrial strains. Although genetically complex, alcohol tolerance can thus be dominated by a single cellular process, one controlled by a major physicochemical component but amenable to biological augmentation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401034/" 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/PMC4401034/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lam, Felix H -- Ghaderi, Adel -- Fink, Gerald R -- Stephanopoulos, Gregory -- R01 GM035010/GM/NIGMS NIH HHS/ -- R01-GM035010/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 3;346(6205):71-5. doi: 10.1126/science.1257859. Epub 2014 Oct 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. Whitehead Institute for Biomedical Research, Cambridge, MA, USA. ; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. ; Whitehead Institute for Biomedical Research, Cambridge, MA, USA. gfink@wi.mit.edu gregstep@mit.edu. ; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. gfink@wi.mit.edu gregstep@mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25278607" target="_blank"〉PubMed〈/a〉
    Keywords: *Biofuels ; Cation Transport Proteins/genetics ; Cell Culture Techniques ; Cell Membrane/metabolism ; Chemical Engineering ; *Drug Resistance, Fungal/genetics ; Ethanol/*metabolism/pharmacology ; Fermentation ; Genetic Engineering ; Glucose/metabolism ; Hydrogen-Ion Concentration ; Phosphates/*metabolism ; Potassium Compounds/*metabolism ; Proton Pumps/genetics ; Proton-Translocating ATPases/genetics ; Saccharomyces cerevisiae/drug effects/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Up-Regulation ; Xylose/metabolism
    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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  • 3
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    Killer whale presence in relation to naval sonar activity and prey abundance in northern Norway (2013)
    Oxford University Press
    Details
    Publication Date: 2013-10-15
    Description: Kuningas, S., Kvadsheim, P. H., Lam, F-P. A., and Miller, P. J. O. 2013. Killer whale presence in relation to naval sonar activity and prey abundance in northern Norway. – ICES Journal of Marine Science, 70: . In this study, retrospective data on naval sonar activity and prey abundance were correlated with killer whale sightings within a fjord basin in northern Norway. In addition, passive acoustic and visual marine mammal surveys were conducted before, during, and after a specific navy exercise in 2006. Herring abundance was the main factor affecting killer whale presence. Naval sonar, either operational navy sonar exercises (Flotex) or experimental sonar activity (CEE) alone, did not explain killer whale occurrence. However, naval sonar activity during a period of low prey availability seemed to have had a negative effect on killer whale presence. We conclude that the level of reaction to sonar can be influenced by multiple factors, including availability of prey.
    Print ISSN: 1054-3139
    Electronic ISSN: 1095-9289
    Topics: Biology , Geosciences , Physics
    Published by Oxford University Press
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  • 4
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    Bottlenose whales and noise (2015)
    Royal Society
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    Publication Date: 2015-06-27
    Description: Although northern bottlenose whales were the most heavily hunted beaked whale, we have little information about this species in its remote habitat of the North Atlantic Ocean. Underwater anthropogenic noise and disruption of their natural habitat may be major threats, given the sensitivity of other beaked whales to such noise disturbance. We attached dataloggers to 13 northern bottlenose whales and compared their natural sounds and movements to those of one individual exposed to escalating levels of 1–2 kHz upsweep naval sonar signals. At a received sound pressure level (SPL) of 98 dB re 1 μPa, the whale turned to approach the sound source, but at a received SPL of 107 dB re 1 μPa, the whale began moving in an unusually straight course and then made a near 180° turn away from the source, and performed the longest and deepest dive (94 min, 2339 m) recorded for this species. Animal movement parameters differed significantly from baseline for more than 7 h until the tag fell off 33–36 km away. No clicks were emitted during the response period, indicating cessation of normal echolocation-based foraging. A sharp decline in both acoustic and visual detections of conspecifics after exposure suggests other whales in the area responded similarly. Though more data are needed, our results indicate high sensitivity of this species to acoustic disturbance, with consequent risk from marine industrialization and naval activity.
    Keywords: environmental science, behaviour, biomechanics
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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