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 S. cerevisiae . The SWI/SNF chromatin remodeling complex is a key mediator of this transcriptional response. We found that a glutamine-rich low complexity sequence (QLC) in the SNF5 subunit of this complex, and histidines within this sequence, were required for efficient transcriptional reprogramming during carbon starvation. Furthermore, the SNF5 QLC mediated pH-dependent recruitment of SWI/SNF to a model promoter in vitro. 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.