S- adenosyl methionine (SAM) donates methyl groups to histones modified during gene regulatory processes. SAM is produced by the 1-carbon cycle and this interaction provides a key link between metabolic status and transcriptional control. We previously found that RNA interference with
sams-1, one of the four SAM synthases in Caenorhabditis elegans, reduces SAM levels as well histone H3 lysine 4 methylation (H3K4me3) in intestinal cells.
sams-1 deficient animals also have altered stress responses. They are unable to accumulate H3K4me3 at promoters of bacterial response genes, upregulate these genes or survive pathogenic challenge. In contrast,
sams-1 animals have enhanced survival during heat shock and regulate heat shock gene expression normally, although metabolic gene expression is broadly downregulated. Several lines of evidence suggest SAM from a distinct synthase may be important. First, interference with the H3K4me3 transferase
set-16 had reduced survival in heat shock. Second, H3K4me3 levels recovered in heat shock in
sams-1 animals, suggesting SAM from a distinct synthase and/or activity histone modifying enzymes could contribute to this stress response. Here, we show that
sams-1 and
sams-4 have distinct roles in the heat shock response, showing that the enzymatic source of SAM is a critical predictor of SAM function. Loss of
sams-4 is distinct from
sams-1 in several critical areas.
sams-4 animals survive poorly after heat shock and is necessary for the recovery of H3K4me3 after heat shock. Next,
sams-4(RNAi) animals do not exhibit the same reductions in metabolic gene expression during heat shock. Finally,
sams-1 and
sams-4 RNAi animals have distinct patterns of H3K4me3 in both basal and heat shocked conditions in CUT&Tag assay measuring genome wide H3K4me3, with
sams-1 animals losing enrichment at metabolic genes, similar to reductions in these genes in RNA seq. Taken together, this shows that the enzymatic source of SAM influences H3K4me3 patterns, gene expression patterns and physiological response to stress.