It is increasingly appreciated that intracellular pH changes are important biological signals. This motivates the elucidation of molecular mechanisms of pH-sensing. We determined that a nucleocytoplasmic pH oscillation was required for the transcriptional response to carbon starvation in Saccharomyces cerevisiae. The SWI/SNF chromatin remodeling complex is a key mediator of this transcriptional response. A glutamine-rich low complexity domain (QLC) in the SNF5 subunit of this complex, and histidines within this sequence, were required for efficient transcriptional reprogramming. Furthermore, the SNF5 QLC mediated pH-dependent recruitment of SWI/SNF to an acidic transcription factor in a reconstituted nucleosome remodeling assay. Simulations showed that protonation of histidines within the SNF5 QLC lead to conformational expansion, providing a potential biophysical mechanism for regulation of these interactions. Together, our results indicate that that pH changes are a second messenger for transcriptional reprogramming during carbon starvation, and that the SNF5 QLC acts as a pH-sensor.
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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