Center for Science and Engineering of Living Systems (CSELS), Washington University in St. Louis, St Louis, United States; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, United States
Craig L Peterson
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
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.
