Methionine availability influences essential H3K36me3 dynamics during cell differentiation [ChIP-seq]
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ABSTRACT:
PROVIDER: PRJNA1042644 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR26874169.fastq.gz | Fastqsanger.gz | |||
| SRR26874170.fastq.gz | Fastqsanger.gz | |||
| SRR26874171.fastq.gz | Fastqsanger.gz | |||
| SRR26874172.fastq.gz | Fastqsanger.gz | |||
| SRR26874173.fastq.gz | Fastqsanger.gz |
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Project description:Methionine availability influences essential H3K36me3 dynamics during cell differentiation
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Project description:Methionine availability influences essential H3K36me3 dynamics during cell differentiation [ATAC-seq]
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Project description:Histone modifications are integral to epigenetics through their influence on gene expression and cellular status. While it's established that metabolism, including methionine metabolism, can impact histone methylation, the direct influence of methionine availability on crucial histone marks that determine the epigenomic process remains poorly understood. In this study, we demonstrate that methionine, through its metabolic product, S-adenosylmethionine (SAM), dynamically regulates H3K36me3, a cancer-associated histone modification known to influence cellular status, and myogenic differentiation of mouse myoblast cells. We further demonstrate that the methionine-dependent effects on differentiation are mediated in part through the histone methyltransferase SETD2, which senses methionine levels. Additionally, methionine restriction leads to preferential decreases in H3K36me3 abundance and genome accessibility of genes involved in myogenic differentiation. Importantly, the effects of methionine restriction on differentiation and chromatin accessibility can be phenocopied by the deletion of Setd2. Collectively, this study demonstrates that methionine metabolism through its ability to be sensed by chromatin modifying enzymes can have a direct role in influencing cell fate determination.
2023-11-30 | GSE248197 | GEO
Project description:Histone modifications are integral to epigenetics through their influence on gene expression and cellular status. While it's established that metabolism, including methionine metabolism, can impact histone methylation, the direct influence of methionine availability on crucial histone marks that determine the epigenomic process remains poorly understood. In this study, we demonstrate that methionine, through its metabolic product, S-adenosylmethionine (SAM), dynamically regulates H3K36me3, a cancer-associated histone modification known to influence cellular status, and myogenic differentiation of mouse myoblast cells. We further demonstrate that the methionine-dependent effects on differentiation are mediated in part through the histone methyltransferase SETD2, which senses methionine levels. Additionally, methionine restriction leads to preferential decreases in H3K36me3 abundance and genome accessibility of genes involved in myogenic differentiation. Importantly, the effects of methionine restriction on differentiation and chromatin accessibility can be phenocopied by the deletion of Setd2. Collectively, this study demonstrates that methionine metabolism through its ability to be sensed by chromatin modifying enzymes can have a direct role in influencing cell fate determination.
2023-11-30 | GSE248198 | GEO
Project description:Histone modifications are integral to epigenetics through their influence on gene expression and cellular status. While it's established that metabolism, including methionine metabolism, can impact histone methylation, the direct influence of methionine availability on crucial histone marks that determine the epigenomic process remains poorly understood. In this study, we demonstrate that methionine, through its metabolic product, S-adenosylmethionine (SAM), dynamically regulates H3K36me3, a cancer-associated histone modification known to influence cellular status, and myogenic differentiation of mouse myoblast cells. We further demonstrate that the methionine-dependent effects on differentiation are mediated in part through the histone methyltransferase SETD2. Methionine restriction leads to preferential decreases in H3K36me3 abundance and genome accessibility of genes involved in myogenic differentiation. Importantly, the effects of methionine restriction on differentiation and chromatin accessibility can be phenocopied by the deletion of Setd2. Collectively, this study demonstrates that methionine metabolism through its ability to be sensed by chromatin modifying enzymes can have a direct role in influencing cell fate determination.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2023-11-30 | GSE248199 | GEO
Project description:T cell receptor (TCR) activation is regulated in multifaceted ways, including niche-specific nutrient availability. We investigated how methionine (Met) availability and TCR signaling interplay in the earliest events of T cell activation to affect subsequent cell fate. Limiting Met during the initial 30 minutes of TCR engagement increased Ca2+ influx, NFAT1 (Nfatc2) activation and promoter occupancy leading to T cell exhaustion. We identified changes in the protein arginine methylome during the initial TCR engagement and discovered a novel arginine methylation of a Ca2+-activated potassium transporter, KCa3.1, which regulates Ca2+-mediated NFAT1 signaling for optimal activation. Ablation of KCa3.1 arginine methylation increased NFAT1 nuclear localization, rendering T cells dysfunctional in murine tumour and infection models. Furthermore, acute Met supplementation at early stages reduced nuclear NFAT1 in tumour-infiltrating T cells and augmented their anti-tumour activity. Our findings identify a metabolic event occurring early after T cell activation that influences cell fate.
2025-05-29 | GSE221350 | GEO
Project description:Early methionine availability attenuates T cell exhaustion
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Project description:Cancer cells exhibit a well-documented, yet poorly understood, dependence on exogenous methionine, despite retaining the capacity to convert homocysteine to methionine. In contrast, non-tumorigenic cells can proliferate when methionine is replaced by homocysteine. To investigate the mechanistic basis of this methionine dependence, we examined how methionine metabolism impacts cell cycle progression. We identified carboxy-methylation of the catalytic subunit of Protein Phosphatase 2A (PP2A) as a critical node linking methionine availability to proliferation. PP2A methylation was found to be highly sensitive to intracellular S-adenosylmethionine (SAM) levels, with reduced methylation correlating with impaired proliferation under methionine restriction. Overexpression of Protein Phosphatase Methylesterase-1 (PME-1), which demethylates PP2A, or expression of a Leu309-deleted PP2A mutant that mimics the demethylated form, was sufficient to reduce proliferation even in methionine-independent cells. These findings support a model in which methionine limitation lowers SAM availability, thereby decreasing PP2A methylation and impairing cell cycle progression. Our study reveals a novel mechanistic link between methionine metabolism and the cell cycle and suggests that PP2A methylation plays a key role in the unique methionine dependence of cancer cells.
2025-07-03 | GSE301557 | GEO
Project description:Targeting altered tumor cell metabolism might provide an attractive opportunity for patients with acute myeloid leukemia (AML). An amino acid dropout screen on primary leukemic stem cells and progenitor populations revealed a number of amino acid dependencies, of which methionine was one of the strongest. By using various metabolite rescue experiments, NMR-based metabolite quantifications and 13C-tracing, polysomal profiling, and ChIP-seq, we identified that methionine is used predominantly for protein translation and to provide methyl groups to histones via S-adenosylmethionine for epigenetic marking. H3K36me3 was consistently the most heavily impacted mark following loss of methionine. Methionine depletion also reduced total RNA levels, enhanced apoptosis and induced a cell cycle block. ROS levels were not increased following methionine depletion and replacement of methionine with glutathione or N-acetylcysteine could not rescue phenotypes, excluding a role for methionine in controlling redox balance control in AML. Although considered to be an essential amino acid, methionine can be recycled from homocysteine. We uncovered that this is primarily performed by the enzyme methionine synthase and only when methionine availability becomes limiting. In vivo, dietary methionine starvation was not only tolerated by mice, but also significantly delayed both cell line and patient-derived AML progression. Finally, we show that inhibition of the H3K36-specific methyltransferase SETD2 phenocopies much of the cytotoxic effects of methionine depletion, providing a more targeted therapeutic approach. In conclusion, we show that methionine depletion is a vulnerability in AML that can be exploited therapeutically, and we provide mechanistic insight into how cells metabolize and recycle methionine.
2022-12-21 | GSE220236 | GEO