Abstract
Expression of an individual gene can vary considerably among genetically identical cells because of stochastic fluctuations in transcription. However, proteins comprising essential complexes or pathways have similar abundances and lower variability. It is not known whether coordination in the expression of subunits of essential complexes occurs at the level of transcription, mRNA abundance or protein expression. To directly measure the level of coordination in the expression of genes, we used highly sensitive fluorescence in situ hybridization (FISH) to count individual mRNAs of functionally related and unrelated genes within single Saccharomyces cerevisiae cells. Our results revealed that transcript levels of temporally induced genes are highly correlated in individual cells. In contrast, transcription of constitutive genes encoding essential subunits of complexes is not coordinated because of stochastic fluctuations. The coordination of these functional complexes therefore must occur post-transcriptionally, and likely post-translationally.
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Change history
12 December 2010
In the version of this article initially published online, the color key in Figure 7c,d was incorrect. The error has been corrected for all versions of this article.
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Acknowledgements
We thank M. Keogh from Albert Einstein College of Medicine for helpful discussions of GAL experiments and for providing reagents to create the HTZ1 deletion strain. We thank D. Botstein and S.J. Silverman from Princeton University for helpful discussions and for providing cells with a doubling time of 14 h, respectively. This work was supported by the United States National Institutes of Health (GM 57071) and the Human Frontier Science Program (T.L.).
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S.J.G. and D.Z. initiated the project. S.J.G. conducted the experiments and data analysis. S.J.G. and T.L. did the numerical simulations and T.L. derived the analytical solution. D.Z. and R.H.S. supervised the project. S.J.G. wrote the paper with editorial help from D.Z., T.L. and R.H.S.
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Supplementary Figures 1–11, Supplementary Table 1 and Supplementary Methods (PDF 2233 kb)
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Gandhi, S., Zenklusen, D., Lionnet, T. et al. Transcription of functionally related constitutive genes is not coordinated. Nat Struct Mol Biol 18, 27–34 (2011). https://doi.org/10.1038/nsmb.1934
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DOI: https://doi.org/10.1038/nsmb.1934
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