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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.

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., Competing Interests: JG, GB, YK, KT, AD, AH, CP, LH No competing interests declared, (© 2022, Gutierrez et al.)