Polyglutamines are known to form aggregates in pathogenic contexts, such as Huntington disease. However, little is known about their normal biological role. We found that the polyglutamine domain of the Snf5 subunit of yeast SWI/SNF complex is required for efficient induction of glucose-repressed genes. Both transient cytosolic acidification and histidines within the polyglutamine domain were required for efficient transcriptional reprogramming. We hypothesized that a pHdependent oligomerization could be important for ADH2 expression. In support of this idea, we found that a synthetic spidroin domain from spider silk, which is soluble at pH 7 but oligomerizes at pH ~6.3, could partially complement the function of the SNF5 polyglutamine domain. These results suggest that the SNF5 polyglutamine domain is a pH-responsive transcriptional regulator, and provide further evidence of an important biological role for polyglutamine domains beyond the disease context.

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