SWI/SNF senses carbon starvation with a pH-sensitive low-complexity sequence

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, was 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 leads to conformational expansion, providing a potential biophysical mechanism for regulation of these interactions. Together, our results indicate that pH changes are a second messenger for transcriptional reprogramming during carbon starvation and that the SNF5 QLC acts as a pH sensor.

Automated summary

It is increasingly recognized that changes in intracellular pH serve as important biological signals. This study focuses on elucidating the molecular mechanisms of pH sensing. The researchers found that a nucleocytoplasmic pH oscillation is crucial for the transcriptional response to carbon starvation in Saccharomyces cerevisiae. They also discovered that the SWI/SNF chromatin remodeling complex plays a key role in this response. Specifically, a glutamine-rich low-complexity domain (QLC) in the SNF5 subunit of this complex, along with histidines within this domain, is essential for efficient transcriptional reprogramming. Additionally, the SNF5 QLC is responsible for the pH-dependent recruitment of SWI/SNF to an acidic transcription factor in a reconstituted nucleosome remodeling assay. Simulations revealed that the protonation of histidines in the SNF5 QLC causes conformational expansion, offering a potential biophysical mechanism for regulating these interactions. Overall, this study suggests that pH changes act as a second messenger for transcriptional reprogramming during carbon starvation, with the SNF5 QLC serving as a pH sensor.