Naturally occurring sequence variation that affects gene expression is an important source of phenotypic differences among individuals within a species. We and others have previously shown that such regulatory variation can occur at the locus as the gene whose expression it affects, and elsewhere in the genome at trans-acting factors. Here we present a genome-wide analysis of local regulatory variation in Saccharomyces cerevisiae. We use genetic linkage analysis to show that a quarter of all yeast genes contain local regulatory variation between two divergent strains. Measurements of allele-specific expression in a diploid hybrid demonstrate that 50-80% of local regulatory polymorphisms affect transcript levels directly in cis, while the rest act in trans, presumably through feedback loops. Sequence analysis reveals that genes subject to local regulatory variation show increased polymorphism in the promoter regions, and that some but not all of this increase is due to polymorphisms in predicted transcription factor binding sites. Increased polymorphism is also found in the 3' untranslated regions of these genes, suggesting that there is a diverse set of mechanisms through which local variation can affect gene expression levels.
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