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Article
Nature Genetics  35, 57 - 64 (2003)
Published online: 3 August 2003; | doi:10.1038/ng1222

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

Gaël Yvert1, 4, Rachel B Brem1, Jacqueline Whittle1, Joshua M Akey1, Eric Foss1, Erin N Smith1, 2, Rachel Mackelprang1, 3 & Leonid Kruglyak1

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

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

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

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

Correspondence should be addressed to Leonid Kruglyak leonid@fhcrc.org
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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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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