The largest SWI/SNF polyglutamine domain is a pH sensor

Polyglutamines are known to form aggregates in pathogenic contexts, such as in Huntington’s disease, however little is known about their role in normal biological processes. We found that a polyglutamine domain in the SNF5 subunit of the yeast SWI/SNF complex, histidines within this sequence, and transient intracellular acidification are required for efficient transcriptional regulation during carbon starvation. We hypothesized that a pH-driven oligomerization of the SNF5 polyglutamine region is required for transcriptional reprogramming. 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. These results suggest that the SNF5 polyglutamine domain acts as a pH-driven transcriptional regulator.