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.
Sequencing data have been deposited in GEO under accession code GSE223597.
C. elegans stress-induced gene expression in low SAM or after histone-methytransferase RNAiNCBI Gene Expression Omnibus. GSE121511.
- Amy K Walker
- Thomas G Fazzio
- Sneha Gopalan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Jan Gruber, Yale-NUS College, Singapore
© 2023, Godbole et al.
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