S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stress

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 hav...

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Published inbioRxiv
Main Authors Godbole, Adwait A, Gopalan, Sneha, Thein-Kim, Nguyen, Munden, Alexander L, Vo, Paula, Lewis, Caroline A, Spinelli, Jessica B, Fazzio, Thomas G, Amy Karol Walker
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 22.01.2023
Subjects
Adenosylmethionine
Aging
Bioinformatics
Carbon cycle
DNA methylation
Gene expression
Heat stress
Life span
Metabolomics
Methionine
Phenotypes
S-Adenosylmethionine
Survival
Temperature effects
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Summary: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.Competing Interest StatementThe authors have declared no competing interest.Footnotes* We have revised the manuscript, adding additional metabolomics and survival data. In addition, we have expanded the methods section for our C. elegans studies as well as the CUT&Tag. Authors have been added to reflect the additional metabolomics and bioinformatics studies.
DOI:10.1101/2022.03.30.486419