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 . The SWI/SNF chromatin remodeling complex is a key mediator of this transcriptional response. A glutamine-rich low-complexity domain (QLC) in the subunit of this complex, and histidines within this sequence, was required for efficient transcriptional reprogramming. Furthermore, the QLC mediated pH-dependent recruitment of to an acidic transcription factor in a reconstituted nucleosome remodeling assay. Simulations showed that protonation of histidines within the 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 QLC acts as a pH sensor.