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

Area of Science:

• Molecular Biology
• Cellular Biology
• Biochemistry

Background:

• Intracellular pH fluctuations serve as critical biological signals.
• Understanding molecular pH sensing mechanisms is essential for biological insights.

Purpose of the Study:

• To investigate the role of nucleocytoplasmic pH oscillations in transcriptional regulation during carbon starvation in Saccharomyces cerevisiae.
• To elucidate the molecular mechanisms by which the SWI/SNF chromatin remodeling complex senses and responds to pH changes.

Main Methods:

• Utilized Saccharomyces cerevisiae as a model organism.
• Investigated the function of the SNF5 subunit's glutamine-rich low-complexity domain (QLC).
• Employed reconstituted nucleosome remodeling assays and molecular simulations.

Main Results:

• A nucleocytoplasmic pH oscillation is required for transcriptional response to carbon starvation.
• The SNF5 QLC, containing specific histidines, is crucial for transcriptional reprogramming.
• The SNF5 QLC mediates pH-dependent SWI/SNF complex recruitment to transcription factors.
• Protonation of histidines in SNF5 QLC induces conformational expansion, suggesting a biophysical sensing mechanism.

Conclusions:

• pH changes act as second messengers in transcriptional reprogramming during carbon starvation.
• The SNF5 QLC functions as a direct pH sensor within the SWI/SNF complex.