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Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors

Nature Genetics volume 35, pages 57–64 (2003)Cite this article

Abstract

Natural genetic variation can cause significant differences in gene expression, but little is known about the polymorphisms that affect gene regulation. We analyzed regulatory variation in a cross between laboratory and wild strains of Saccharomyces cerevisiae. Clustering and linkage analysis defined groups of coregulated genes and the loci involved in their regulation. Most expression differences mapped to trans-acting loci. Positional cloning and functional assays showed that polymorphisms in GPA1 and AMN1 affect expression of genes involved in pheromone response and daughter cell separation, respectively. We also asked whether particular classes of genes were more likely to contain trans-regulatory polymorphisms. Notably, transcription factors showed no enrichment, and trans-regulatory variation seems to be broadly dispersed across classes of genes with different molecular functions.

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Figure 1: Genetic mapping of cluster regulators.
Figure 2: Coding sequence polymorphisms at trans-regulatory loci.
Figure 3: Effect of AMN1 on clumpiness.

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Acknowledgements

We thank J. Delrow, D. Hare, J. Marty and the Fred Hutchinson Cancer Research Center microarray, oligo synthesis and sequencing facilities for technical assistance; M. Eberle and H. Childs for help in manuscript preparation; D. Gottschling and R. Young for discussions; and H. Coller for discussions and a critical reading of the manuscript. G.Y. and R.B. were supported by postdoctoral fellowships from the Human Frontier Science Program and the National Institutes of Health, respectively. This work was supported by the Howard Hughes Medical Institute, of which L.K. is an associate investigator. L.K. is a James S. McDonnell Centennial Fellow.

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Author notes

  1. Gaël Yvert

    Present address: Centre G. Durand, UMR-CNRS 5504, INSA, 135 Ave de Rangueil, 31077, Toulouse, cedex 04, France

Authors and Affiliations

  1. Howard Hughes Medical Institute and Division of Human Biology, Fred Hutchinson Cancer Research Center, Mailstop D4-100, 1100 Fairview Avenue North, Seattle, 98103, Washington, USA

    Gaël Yvert, Rachel B Brem, Jacqueline Whittle, Joshua M Akey, Eric Foss, Erin N Smith, Rachel Mackelprang & Leonid Kruglyak

  2. Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, USA

    Erin N Smith

  3. Department of Genome Sciences, University of Washington, Seattle, Washington, USA

    Rachel Mackelprang

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Correspondence to Leonid Kruglyak.

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Yvert, G., Brem, R., Whittle, J. et al. Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors. Nat Genet 35, 57–64 (2003). https://doi.org/10.1038/ng1222

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