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. Author summary Animals respond to stress by activating suites of protective genes. A specific metabolite, S-adenosylmethionine (SAM), influences how these genes are activated in a variety of stress conditions. SAM is produced by the 1-carbon cycle and is the major donor for methylation reactions. Thus, SAM is used in the modification of histones, DNA, RNA and production of phospholipids. Here, we show that C . elegans with low SAM have reduced responses to a bacterial and toxic stress, but respond normally to heat stress. We also analyzed how animals that have reduced activity in some of the enzymes that use SAM to modify histones might respond to stress. One enzyme, SET-2, was needed only for survival in bacterial stress, whereas the other related enzyme, SET-16, was universally required. The availability of SAM may be affected by diets low in choline or methionine, alcohol or diseases such as cystic fibrosis. Thus, low SAM availability may leave organisms less able to respond to additional stress, which could exacerbate tissue injury or disease progression.
【초록키워드】 Gene Expression, Stress, Genetic, Transcription, fibrosis, alcohol, metabolism, RNA, Disease progression, nucleic acid, DNA, survival, pathogen, animals, animal, response, Gene regulation, cystic fibrosis, group, Enzymes, disease, expression, metabolite, Protective, Donor, Methylation, Bacterial, histone, Phospholipids, Phosphatidylcholine, Heat shock, Acute stress, tissue injury, Caenorhabditis elegans, heat stress, in some, choline, S-adenosylmethionine, methionine, methyl groups, deficiency, Organisms, Regulation, Histones, Reactions, deficiencies, enzyme, organism, transcriptional response, Modification, chromatin, elegans, stress conditions, transcriptional responses, Genes, responses, produced, analyzed, affected, assays, required, reduced, provide, activated, less, variety, respond, activating, elegan, Caenorhabditis elegan, SAM, influence, modify, exacerbate, 【제목키워드】 Gene regulation, Regulation,