The largest SWI/SNF polyglutamine domain is a pH sensor

Abstract

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.

Cellular sensing by phase separation: Using the process, not just the products

“…A similar process was also recently reported for another important stress-associated transcription factor in yeast (74). Snf5, a component of the SWI/SNF complex responsible for the expression of many glucose-repressed genes, has a poly-Q stretch that the authors find is crucial for transcriptional activation.…”

The three faces of Sup35

“…For example, several proteins associated with transcription and chromatin remodeling contain low complexity regions. One protein, Snf5p, is glutamine and asparagine rich and also appears to phase separate in response to pH stress (Gutierrez, Brittingham, Wang, Fenyo, & Holt, ). It is intriguing to speculate that inherent sensing abilities via low complexity regions could provide a wide array of proteins, particularly those involved in global functions such as transcription and translation, with a rapid mechanism for responding to transient stress.…”

Transient intracellular acidification regulates the core transcriptional heat shock response

“…Early work in Drosophila melanogaster produced mixed results: one study indicated that acidification had little impact on the production of heat shock proteins ( Drummond et al, 1986 ), while later work showed that Hsf1 trimerization, a key activation step, could be induced by acidification in vitro ( Zhong et al, 1999 ). More recently, acidification during stress has been shown to influence cell signaling ( Dechant et al, 2010 ; Gutierrez et al, 2017 ) and appears to be cytoprotective ( Munder et al, 2016 ; Joyner et al, 2016 ; Coote et al, 1991 ; Panaretou and Piper, 1990 ). The extent to which this adaptive effect of pH depends on the core transcriptional stress response remains unknown.…”