RRC ID 45554
著者 Ding W, Smulan LJ, Hou NS, Taubert S, Watts JL, Walker AK.
タイトル s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways.
ジャーナル Cell Metab
Abstract 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.
巻・号 22(4)
ページ 633-45
公開日 2015-10-6
DOI 10.1016/j.cmet.2015.07.013
PII S1550-4131(15)00342-3
PMID 26321661
PMC PMC4598287
MeSH Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans / microbiology Caenorhabditis elegans Proteins / antagonists & inhibitors Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Histone Methyltransferases Histone-Lysine N-Methyltransferase / metabolism Histones / metabolism Immunity, Innate* Liver / metabolism Methionine Adenosyltransferase / antagonists & inhibitors Methionine Adenosyltransferase / genetics Methionine Adenosyltransferase / metabolism Mitogen-Activated Protein Kinases / metabolism Phosphatidylcholines / metabolism Promoter Regions, Genetic Pseudomonas aeruginosa / physiology RNA Interference RNA, Small Interfering / metabolism S-Adenosylmethionine / metabolism* Signal Transduction p38 Mitogen-Activated Protein Kinases / metabolism
IF 21.567
引用数 40
WOS 分野 ENDOCRINOLOGY & METABOLISM CELL BIOLOGY
リソース情報
線虫 tm3036