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 the 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-responsive phenotypes, but specific mechanistic links have been difficult to identify because methylation is a widely distributed modification. Here we find that two SAM synthases in Caenorhabditis elegans, SAMS-1 and SAMS-4, contribute differently to modification of H3K4me3, gene expression and survival in the heat stress response. Both synthases are expressed in intestinal and hypodermal cells, which are major stress responsive tissues. We find that SAM is provisioned to distinct targets, even within the same methylation mark, depending on the enzymatic source. This suggests that determining how methyl donors are provided will broaden insight into 1CC functions in aging and stress.