Studies of natural populations of many organisms have shown that traits are often complex, caused by contributions of mutations in multiple genes. In contrast, genetic studies in the laboratory primarily focus on studying the phenotypes caused by mutations in a single gene. However, the single mutation approach may be limited with respect to the breadth and degree of new phenotypes that can be found. We have taken the approach of isolating complex, or polygenic mutants in the lab to study the regulation of transcriptional activation distance in @entity375 . While most aspects of eukaryotic transcription are conserved from @entity375 to @entity1 , transcriptional activation distance is not. In @entity375 , the upstream activating sequence (UAS) is generally found within 450 base pairs of the @entity1021 ( @entity1021 ) and when the UAS is moved too far away, activation no longer occurs. In contrast, metazoan enhancers can activate from as far as several hundred kilobases from the @entity1021 . Previously, we identified single mutations that allow transcription activation to occur at a greater-than-normal distance from the @entity11870 UAS. As the single mutant phenotypes were weak, we have now isolated polygenic mutants that possess strong long-distance phenotypes. By identification of the causative mutations we have accounted for most of the heritability of the phenotype in each strain and have provided evidence that the Mediator coactivator complex plays both positive and negative roles in the regulation of transcription activation distance.

Analysis of Polygenic Mutants Suggests a Role for Mediator in Regulating Transcriptional Activation Distance in XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity375 :: ('4932', 'Species') :: ['yeast', 'Saccharomyces cerevisiae'] @entity11870 :: ('852308(Tax:4932)', 'Gene') :: ['GAL1'] @entity1021 :: ('MESH:D020922', 'Disease') :: ['transcription start site', 'TSS']
@entity375 :: (4932,Species) :: ['Saccharomyces cerevisiae']
