s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways

Wei Ding; Lorissa J Smulan; Nicole S Hou; Stefan Taubert; Jennifer L Watts; Amy K Walker

doi:10.1016/j.cmet.2015.07.013

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s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways

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s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways

Wei Ding, Lorissa J Smulan, Nicole S Hou, Stefan Taubert, Jennifer L Watts and Amy K Walker

Cell metabolism, Vol.22(4), pp.633-645

10/06/2015

DOI: https://doi.org/10.1016/j.cmet.2015.07.013

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https://hdl.handle.net/2376/103672

PMCID: PMC4598287

PMID: 26321661

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Abstract

Caenorhabditis elegans - microbiology

Promoter Regions, Genetic

Caenorhabditis elegans - metabolism

Signal Transduction

Liver - metabolism

Caenorhabditis elegans Proteins - metabolism

Methionine Adenosyltransferase - metabolism

Pseudomonas aeruginosa - physiology

Immunity, Innate

Phosphatidylcholines - metabolism

Methionine Adenosyltransferase - genetics

Animals

Caenorhabditis elegans Proteins - antagonists & inhibitors

Histone-Lysine N-Methyltransferase - metabolism

Methionine Adenosyltransferase - antagonists & inhibitors

RNA Interference

p38 Mitogen-Activated Protein Kinases - metabolism

Histones - metabolism

Caenorhabditis elegans Proteins - genetics

S-Adenosylmethionine - metabolism

Mitogen-Activated Protein Kinases - metabolism

RNA, Small Interfering - metabolism

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.

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Title: s-Adenosylmethionine Levels Govern Innate Immunity through Distinct Methylation-Dependent Pathways
Creators: Wei Ding - Program in Molecular Medicine, UMass Worcester, 373 Plantation Street, Worcester, MA 01605, USA
Lorissa J Smulan - Program in Molecular Medicine, UMass Worcester, 373 Plantation Street, Worcester, MA 01605, USA
Nicole S Hou - Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics (CMMT) and Child & Family Research Institute (CFRI), University of British Columbia (UBC), Vancouver, BC V5Z 4H4, Canada
Stefan Taubert - Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics (CMMT) and Child & Family Research Institute (CFRI), University of British Columbia (UBC), Vancouver, BC V5Z 4H4, Canada
Jennifer L Watts - School of Molecular Biosciences, Washington State University, Pullman, WA 99164-6340, USA
Amy K Walker - Program in Molecular Medicine, UMass Worcester, 373 Plantation Street, Worcester, MA 01605, USA. Electronic address: amy.walker@umassmed.edu
Publication Details: Cell metabolism, Vol.22(4), pp.633-645
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: R01 DK084352 / NIDDK NIH HHS MOP-93713 / Canadian Institutes of Health Research R01DK084352 / NIDDK NIH HHS R01 DK074114 / NIDDK NIH HHS R01DK74114 / NIDDK NIH HHS P40 OD010440 / NIH HHS
Identifiers: 99900546790701842
Language: English
Resource Type: Journal article