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PMID: 18818649 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Frequency-modulated nuclear localization bursts coordinate gene regulation.

Nature ·Vol. 455 ·No. 7212 ·2008-09-25 ·Pages 485-90

Cai L, Dalal CK, Elowitz MB

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.

MeSH Terms
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
Chemicals
CRZ1 protein, S cerevisiae DNA-Binding Proteins MSN2 protein, S cerevisiae Saccharomyces cerevisiae Proteins Trans-Activators Transcription Factors Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Cai Long
Howard Hughes Medical Institute, Division of Biology and Department of Applied Physics, California Institute of Technology, M/C 114-96, Pasadena, California 91125, USA.
Dalal Chiraj K
Elowitz Michael B
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/nature07292
Published
2008-09-25
Pages
485-90
Language
English
Region
England
NLM ID
0410462
PMCID
PMC2695983
Subset
IM
Grants
NIGMS NIH HHS · P50 GM068763 · United States
NIGMS NIH HHS · P50 GM068763-050005 · United States
NIGMS NIH HHS · R01 GM079771-02 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R01GM079771 · United States
NIGMS NIH HHS · R01 GM079771 · United States
External Links
PubMed source DOI: 10.1038/nature07292 PMC Full Text View journal details
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