Methionine Metabolism Shapes T Helper Cell Responses through Regulation of Epigenetic Reprogramming.

Publication date: Feb 04, 2020

Epigenetic modifications on DNA and histones regulate gene expression by modulating chromatin accessibility to transcription machinery. Here we identify methionine as a key nutrient affecting epigenetic reprogramming in CD4 T helper (Th) cells. Using metabolomics, we showed that methionine is rapidly taken up by activated T cells and serves as the major substrate for biosynthesis of the universal methyl donor S-adenosyl-L-methionine (SAM). Methionine was required to maintain intracellular SAM pools in T cells. Methionine restriction reduced histone H3K4 methylation (H3K4me3) at the promoter regions of key genes involved in Th17 cell proliferation and cytokine production. Applied to the mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis), dietary methionine restriction reduced the expansion of pathogenic Th17 cells in vivo, leading to reduced T cell-mediated neuroinflammation and disease onset. Our data identify methionine as a key nutritional factor shaping Th cell proliferation and function in part through regulation of histone methylation.

Roy, D.G., Chen, J., , Mamane, Ma, E.H., Muhire, B.M., Sheldon, R.D., Shorstova, T., Koning, R., Johnson, R.M., Esaulova, E., Williams, K.S., Hayes, S., Steadman, M., Samborska, B., Swain, A., Daigneault, A., , Chubukov, Roddy, T.P., Foulkes, W., Pospisilik, J.A., Bourgeois-Daigneault, M.C., Artyomov, M.N., Witcher, M., Krawczyk, C.M., Larochelle, C., and Jones, R.G. Methionine Metabolism Shapes T Helper Cell Responses through Regulation of Epigenetic Reprogramming. 20135. 2020 Cell Metab (31):2.

Concepts Keywords
Accessibility Branches of biology
Biosynthesis Genetics
CD4 Posttranslational modification
Chromatin Organic reactions
Cytokine Histone methylation
Epigenetic Methionine
Histone H3K4me3
Histones Metabolomics
Intracellular
Metabolomics
Methionine
Methyl
Methylation
Multiple Sclerosis
Nutrient
Pathogenic
Substrate
Th17
Transcription

Semantics

Type Source Name
drug DRUGBANK Methionine
drug DRUGBANK Ademetionine
pathway REACTOME Methylation
disease MESH multiple sclerosis
disease MESH experimental autoimmune encephalomyelitis
disease MESH inflammation

Original Article

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