Project description:The goals of this study were to compare the distribution of H3K4me3 before and after methionine restriction to understand how nutrient availability and alterations in methionine metabolism affect the epigenetic state and regulate gene transcription. To do this we performed ChIP-seq with an H3K4me3 antibody and RNA-seq using PolyA+ mRNA.
Project description:In this study, we compared genomic H3K4me3 and gene expression profiles before and after methionine restriction in human cancer cells and mouse liver. The goals are to understand the influences of nutrient availability on genomic architecture of histone modification and gene expression.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Epigenetic modifications on DNA and histones regulate gene expression by modulating chromatin accessibility to transcription machinery. Chromatin-modifying enzymes are dependent on metabolic intermediates for chromatin remodeling, linking nutrient availability and cellular metabolism to the cellular epigenetic landscape. Here we identify methionine as a key nutrient affecting T cell epigenetic reprogramming in CD4+ T helper (Th) cells. Using metabolomic approaches, we showed that methionine is rapidly taken up by activated T cells and then serves as the major substrate for the biosynthesis of S-adenosyl-L-methionine (SAM), the universal methyl donor for cellular methyltransferases. Conversely, methionine restriction (MR) depletes intracellular SAM pools, reduces global histone H3K4 methylation (H3K4me3) in T cells, and reduces H3K4me3 levels at the promoter regions of key genes involved in CD4+ 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. Overall our data identify methionine as a key nutritional factor that shapes T cell proliferation, differentiation, and function in part through regulation of histone methylation in T cells.
Project description:Epigenetic modifications on DNA and histones regulate gene expression by modulating chromatin accessibility to transcription machinery. Chromatin-modifying enzymes are dependent on metabolic intermediates for chromatin remodeling, linking nutrient availability and cellular metabolism to the cellular epigenetic landscape. Here we identify methionine as a key nutrient affecting T cell epigenetic reprogramming in CD4+ T helper (Th) cells. Using metabolomic approaches, we showed that methionine is rapidly taken up by activated T cells and then serves as the major substrate for the biosynthesis of S-adenosyl-L-methionine (SAM), the universal methyl donor for cellular methyltransferases. Conversely, methionine restriction (MR) depletes intracellular SAM pools, reduces global histone H3K4 methylation (H3K4me3) in T cells, and reduces H3K4me3 levels at the promoter regions of key genes involved in CD4+ 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. Overall our data identify methionine as a key nutritional factor that shapes T cell proliferation, differentiation, and function in part through regulation of histone methylation in T cells.
