Publication Date:
2008-09-27
Description:
In yeast, the transcription factor Crz1 is dephosphorylated and translocates into the nucleus in response to extracellular calcium. Here we show, using time-lapse microscopy, that Crz1 exhibits short bursts of nuclear localization (typically lasting 2 min) that occur stochastically in individual cells and propagate to the expression of downstream genes. Strikingly, calcium concentration controls the frequency, but not the duration, of localization bursts. Using an analytic model, we also show that this frequency modulation of bursts ensures proportional expression of multiple target genes across a wide dynamic range of expression levels, independent of promoter characteristics. We experimentally confirm this theory with natural and synthetic Crz1 target promoters. Another stress-response transcription factor, Msn2, exhibits similar, but largely uncorrelated, localization bursts under calcium stress suggesting that frequency-modulation regulation of localization bursts may be a general control strategy used by the cell to coordinate multi-gene responses to external signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695983/" 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/PMC2695983/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cai, Long -- Dalal, Chiraj K -- Elowitz, Michael B -- P50 GM068763/GM/NIGMS NIH HHS/ -- P50 GM068763-050005/GM/NIGMS NIH HHS/ -- R01 GM079771/GM/NIGMS NIH HHS/ -- R01 GM079771-02/GM/NIGMS NIH HHS/ -- R01GM079771/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Sep 25;455(7212):485-90. doi: 10.1038/nature07292.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Division of Biology and Department of Applied Physics, California Institute of Technology, M/C 114-96, Pasadena, California 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18818649" target="_blank"〉PubMed〈/a〉
Keywords:
Active Transport, Cell Nucleus/drug effects
;
Calcium/metabolism/pharmacology
;
Cell Nucleus/drug effects/*metabolism
;
DNA-Binding Proteins/metabolism
;
*Gene Expression Regulation, Fungal/drug effects
;
Models, Genetic
;
Phosphorylation/drug effects
;
Promoter Regions, Genetic/genetics
;
Reproducibility of Results
;
Saccharomyces cerevisiae/*cytology/drug effects/*genetics
;
Saccharomyces cerevisiae Proteins/*metabolism
;
Stochastic Processes
;
Time Factors
;
Trans-Activators/*metabolism
;
Transcription Factors/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
