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Interspecies variation reveals a conserved repressor of -specific genes in Saccharomyces yeasts

Department of Molecular and Cell Biology, and California Institute for Quantitative Biosciences, University of California at Berkeley, Berkeley, California 94720, USA

The mating-type determination circuit in Saccharomyces yeast serves as a classic paradigm for the genetic control of cell type in all eukaryotes. Using comparative genetics, we discovered a central and conserved, yet previously undetected, component of this genetic circuit: active repression of -specific genes in a cells. Upon inactivation of the SUM1 gene in Saccharomyces bayanus, a close relative of Saccharomyces cerevisiae, a cells acquired mating characteristics of cells and displayed autocrine activation of their mating response pathway. Sum1 protein bound to the promoters of -specific genes, repressing their transcription. In contrast to the standard model, 1 was important but not required for -specific gene activation and mating of cells in the absence of Sum1. Neither Sum1 protein expression, nor its association with target promoters was mating-type-regulated. Thus, the 1/Mcm1 coactivators did not overcome repression by occluding Sum1 binding to DNA. Surprisingly, the mating-type regulatory function of Sum1 was conserved in S. cerevisiae. We suggest that a comprehensive understanding of some genetic pathways may be best attained through the expanded phenotypic space provided by study of those pathways in multiple related organisms.

[Keywords: Sum1; natural variation; cell-type determination; gene regulation]

Received December 5, 2007; revised version accepted April 11, 2008.

E-MAIL jrine{at}berkeley.edu; FAX (510) 666-2768.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1640008.

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