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

  1. J Ignacio Gutierrez
  2. Gregory P Brittingham
  3. Yonca B Karadeniz
  4. Kathleen D Tran
  5. Arnob Dutta
  6. Alex S Holehouse
  7. Craig L Peterson
  8. Liam J Holt  Is a corresponding author
  1. Weill Cornell Medical College, United States
  2. New York University Langone Health, United States
  3. University of Massachusetts Medical School, United States
  4. University of Rhode Island, United States
  5. Washington University in St. Louis, United States

Abstract

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, were 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 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.

Data availability

Simulation code and details can be found at:https://github.com/holehouse-lab/supportingdata/tree/master/2021/Gutierrez_QLC_2021RNA-seq R-code can be found at:https://github.com/gbritt/SWI_SNF_pH_Sensor_RNASeqRNA-seq datasets are depositied at GEO accession number GSE174687https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE174687

The following data sets were generated

Article and author information

Author details

  1. J Ignacio Gutierrez

    Weill Cornell Medical College, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9017-8384
  2. Gregory P Brittingham

    Institute for Systems Genetics, New York University Langone Health, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yonca B Karadeniz

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8299-551X
  4. Kathleen D Tran

    Department of Cell and Molecular Biology, University of Rhode Island, South Kingstown, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Arnob Dutta

    Department of Cell and Molecular Biology, University of Rhode Island, South Kingstown, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Alex S Holehouse

    Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4155-5729
  7. Craig L Peterson

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Liam J Holt

    Institute for Systems Genetics, New York University Langone Health, New York, United States
    For correspondence
    Liam.Holt@nyulangone.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4002-0861

Funding

Becas Chile

  • J Ignacio Gutierrez

National Science Foundation (Graduate Research Fellows Program)

  • Gregory P Brittingham

Pershing Square Sohn Cancer Research Award

  • Liam J Holt

National Cancer Institute (R37 CA240765)

  • Liam J Holt

National Institute of General Medical Sciences (R01 GM132447)

  • Liam J Holt

American Cancer Society Cornelia T. Bailey Foundation Research Scholar Grant (RSG-19-073-01-TBE)

  • Liam J Holt

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Alan G Hinnebusch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States

Publication history

  1. Preprint posted: March 3, 2021 (view preprint)
  2. Received: May 19, 2021
  3. Accepted: February 6, 2022
  4. Accepted Manuscript published: February 7, 2022 (version 1)
  5. Version of Record published: March 2, 2022 (version 2)

Copyright

© 2022, Gutierrez et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. J Ignacio Gutierrez
  2. Gregory P Brittingham
  3. Yonca B Karadeniz
  4. Kathleen D Tran
  5. Arnob Dutta
  6. Alex S Holehouse
  7. Craig L Peterson
  8. Liam J Holt
(2022)
SWI/SNF senses carbon starvation with a pH-sensitive low complexity sequence
eLife 11:e70344.
https://doi.org/10.7554/eLife.70344

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