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Biochemical interactions between cis-regulatory DNA sequences and trans-regulatory gene products suggest that cis- and trans-acting polymorphisms may interact genetically. Here we present a strategy to test this hypothesis by comparing the relative cis-regulatory activity of two alleles in different genetic backgrounds. Of the eight genes surveyed in this study, five were affected by trans-acting variation that altered total transcript levels, two of which were also affected by differences in cis-regulation. The presence of trans-acting variation had no effect on relative cis-regulatory activity, showing that cis-regulatory polymorphisms can function independently of trans-regulatory variation. The frequency of such independent interactions on a genomic scale is yet to be determined.

Independent Effects of cis- and trans-regulatory Variation on Gene Expression in Drosophila melanogaster