Program in Molecular Medicine; Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine
Amino Acids, Peptides, and Proteins | Biochemical Phenomena, Metabolism, and Nutrition | Biochemistry | Cellular and Molecular Physiology | Enzymes and Coenzymes | Genetic Phenomena | Genetics and Genomics | Nucleic Acids, Nucleotides, and Nucleosides
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.
RNA interference, Gene expression, Pseudomonas aeruginosa, Gene regulation, Caenorhabditis elegans, Thermal stresses, Methyltransferases, Transcriptional control
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Copyright: © 2018 Ding et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS Genet. 2018 Nov 28;14(11):e1007812. doi: 10.1371/journal.pgen.1007812. eCollection 2018 Nov. Link to article on publisher's site
Ding W, Higgins DP, Yadav DK, Godbole AA, Pukkila-Worley R, Walker AK. (2018). Stress-responsive and metabolic gene regulation are altered in low S-adenosylmethionine. Open Access Articles. https://doi.org/10.1371/journal.pgen.1007812. Retrieved from https://escholarship.umassmed.edu/oapubs/3679
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