Citation | Ding W, Smulan LJ, Hou NS, Taubert S, Watts JL, Walker AK. s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways. Cell Metab, 2015. |
PubMed ID | 26321661 |
Short Description | s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways. GEO Record: GSE70692 Platform: GPL19230 Download gene-centric, log2 transformed data: WBPaper00048490.ce.mr.csv |
# of Conditions | 12 |
Full Description
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s-adenosylmethionine (SAM) is the sole methyl donor modifying histones, nucleic acids, and phospholipids. Its fluctuation affects hepatic phosphatidylcholine (PC) synthesis or may be linked to variations in DNA or histone methylation. Physiologically, low SAM is associated with lipid accumulation, tissue injury, and immune responses in fatty liver disease. However, molecular connections among SAM limitation, methyltransferases, and disease-associated phenotypes are unclear. We find that low SAM can activate or attenuate Caenorhabditis elegans immune responses. Immune pathways are stimulated downstream of PC production on a non-pathogenic diet. In contrast, distinct SAM-dependent mechanisms limit survival on pathogenic Pseudomonas aeruginosa. C. elegans undertakes a broad transcriptional response to pathogens and we find that low SAM restricts H3K4me3 at Pseudomonas-responsive promoters, limiting their expression. Furthermore, this response depends on the H3K4 methyltransferase set-16/MLL. Thus, our studies provide molecular links between SAM and innate immune functions and suggest that SAM depletion may limit stress-induced gene expression. Experimental Details: WBPaper00048490:empty-vector_repA WBPaper00048490:empty-vector_repB WBPaper00048490:empty-vector_repC WBPaper00048490:empty-vector_choline_repA WBPaper00048490:empty-vector_choline_repB WBPaper00048490:empty-vector_choline_repC WBPaper00048490:sams-1(RNAi)_repA WBPaper00048490:sams-1(RNAi)_repB WBPaper00048490:sams-1(RNAi)_repC WBPaper00048490:sams-1(RNAi)_choline_repA WBPaper00048490:sams-1(RNAi)_choline_repB WBPaper00048490:sams-1(RNAi)_choline_repC. |
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