Abstract

Methylation is a widely occurring modification that requires the methyl donor S-adenosylmethionine (SAM) and acts in regulation of gene expression and other processes. SAM is synthesized from methionine, which is imported or generated through the 1-carbon cycle (1CC). Alterations in 1CC function have clear effects on lifespan and stress responses, but the wide distribution of this modification has made identification of specific mechanistic links difficult. Exploiting a dynamic stress-induced transcription model, we find that two SAM synthases in Caenorhabditis elegans, SAMS-1 and SAMS-4, contribute differently to modification of H3K4me3, gene expression and survival. We find that sams-4 enhances H3K4me3 in heat shocked animals lacking sams-1, however, sams-1 cannot compensate for sams-4, which is required to survive heat stress. This suggests that the regulatory functions of SAM depend on its enzymatic source and that provisioning of SAM may be an important regulatory step linking 1CC function to phenotypes in aging and stress.

Data availability

Sequencing data have been deposited in GEO under accession code GSE223597.

The following previously published data sets were used

Article and author information

Author details

  1. Adwait A Godbole

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sneha Gopalan

    Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Thien-Kim Nguyen

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexander L Munden

    Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Dominique S Lui

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Matthew G Fanelli

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Paula Vo

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

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Jessica B Spinelli

    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Thomas G Fazzio

    3.Department of Molecular, Cell, and Cancer Biology, 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:" 0000-0002-0353-7466
  11. Amy K Walker

    3.Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    amy.walker@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1899-8916

Funding

National Institutes of Health (1R01AG053355)

  • Amy K Walker

National Institutes of Health (R01HD072122)

  • Thomas G Fazzio

National Institutes of Health (K99CA273420)

  • Sneha Gopalan

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

Reviewing Editor

  1. Jan Gruber, Yale-NUS College, Singapore

Version history

  1. Preprint posted: March 30, 2022 (view preprint)
  2. Received: April 15, 2022
  3. Accepted: February 7, 2023
  4. Accepted Manuscript published: February 9, 2023 (version 1)
  5. Accepted Manuscript updated: February 10, 2023 (version 2)
  6. Version of Record published: March 3, 2023 (version 3)

Copyright

© 2023, Godbole 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. Adwait A Godbole
  2. Sneha Gopalan
  3. Thien-Kim Nguyen
  4. Alexander L Munden
  5. Dominique S Lui
  6. Matthew G Fanelli
  7. Paula Vo
  8. Caroline A Lewis
  9. Jessica B Spinelli
  10. Thomas G Fazzio
  11. Amy K Walker
(2023)
S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stress
eLife 12:e79511.
https://doi.org/10.7554/eLife.79511

Share this article

https://doi.org/10.7554/eLife.79511

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