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Frequency-modulated nuclear localization bursts coordinate gene regulation

Cai, Long and Dalal, Chiraj K. and Elowitz, Michael B. (2008) Frequency-modulated nuclear localization bursts coordinate gene regulation. Nature, 455 (7212). pp. 485-491. ISSN 0028-0836. PMCID PMC2695983. https://resolver.caltech.edu/CaltechAUTHORS:CAInat08

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/nature07292DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695983/PubMed CentralArticle
http://rdcu.be/mSDjPublisherFree ReadCube access
ORCID:
AuthorORCID
Cai, Long0000-0002-7154-5361
Dalal, Chiraj K.0000-0002-3624-8409
Elowitz, Michael B.0000-0002-1221-0967
Additional Information:© 2008 Nature Publishing Group. Received 15 May 2008; Accepted 18 July 2008. We thank M. Cyert for the CDRE and Crz1 mutant plasmids, K. Cunningham for the Crz1 overexpression plasmid pLE66, J. Stadler for the pGW845 FRET plasmid, S. Ramanathan for image analysis code, and K. Thorn, C.-L. Guo and L. LeBon for technical assistance. We thank U. Alon, M. Carlson, M. Cyert, H. Garcia, R. Kishony, G. Lahav, J.-G. Ojalvo, I. Riedel-Kruse, B. Shraiman, G. Süel, members of the laboratory, and especially N. Friedman for discussions. L.C. is supported by the Beckman Fellows Program at Caltech. This work was supported by National Institutes of Health grants R01GM079771 and P50 GM068763 for National Centers of Systems Biology, and the Packard Foundation.
Funders:
Funding AgencyGrant Number
NIHR01GM079771
NIHP50 GM068763
David and Lucile Packard FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Subject Keywords:SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTOR; PROTEIN EXPRESSION; BUDDING YEAST; SINGLE-CELL; GLOBAL ANALYSIS; DOCKING SITE; CALCINEURIN; NOISE; OSCILLATIONS
Issue or Number:7212
PubMed Central ID:PMC2695983
Record Number:CaltechAUTHORS:CAInat08
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:CAInat08
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:13259
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:05 Feb 2009 22:41
Last Modified:20 Apr 2020 22:26

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