Stress-responsive and metabolic gene regulation are altered in low S-adenosylmethionine

PLoS Genet. 2018 Nov 28;14(11):e1007812. doi: 10.1371/journal.pgen.1007812. eCollection 2018 Nov.


S-adenosylmethionine (SAM) is a donor which provides the methyl groups for histone or nucleic acid modification and phosphatidylcholine production. SAM is hypothesized to link metabolism and chromatin modification, however, its role in acute gene regulation is poorly understood. We recently found that Caenorhabditis elegans with reduced SAM had deficiencies in H3K4 trimethylation (H3K4me3) at pathogen-response genes, decreasing their expression and limiting pathogen resistance. We hypothesized that SAM may be generally required for stress-responsive transcription. Here, using genetic assays, we show that transcriptional responses to bacterial or xenotoxic stress fail in C. elegans with low SAM, but that expression of heat shock genes are unaffected. We also found that two H3K4 methyltransferases, set-2/SET1 and set-16/MLL, had differential responses to survival during stress. set-2/SET1 is specifically required in bacterial responses, whereas set-16/MLL is universally required. These results define a role for SAM in the acute stress-responsive gene expression. Finally, we find that modification of metabolic gene expression correlates with enhanced survival during stress.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / antagonists & inhibitors
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Genes, Helminth
  • Heat-Shock Response / genetics
  • Histone Code / genetics
  • Histone-Lysine N-Methyltransferase / antagonists & inhibitors
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Pseudomonas aeruginosa / pathogenicity
  • RNA Interference
  • S-Adenosylmethionine / metabolism*
  • Stress, Physiological


  • Caenorhabditis elegans Proteins
  • Nuclear Proteins
  • SET-2 protein, C elegans
  • S-Adenosylmethionine
  • Histone-Lysine N-Methyltransferase