Asparagine starvation on histone methylation and gene expression
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ABSTRACT:
PROVIDER: PRJNA849231 | ENA |
REPOSITORIES: ENA
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Project description:We are determining the impact of asparagine starvation on histone H3K4 trimethylation deposition across the genome and how they may affect the gene expression.
2022-06-16 | GSE206112 | GEO
Project description:We will report the gene expression changes following asparagine depletion in human ALL cell line, RS4;11
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Project description:In Penicillium oxalicum, histone H2B (PDE_01489) was one of the interacting proteins with the methyltransferase LaeA. It suggests that histone H2B may be a direct target of LaeA/Lae1. To verify whether histone H2B is one of the LaeA targets, an in vitro catalytic experiment was performed using Homo sapiens recombinant histone H2B (HsH2B, expressed in Escherichia coli, without histone modification), SAM as substrates, and LaeA. The products were analyzed by LC-MS/MS for histone modifications. Results showed that the mono and di-methylation of lysine 108 and the mono-methylation of lysine 116 were detected.
2021-07-08 | PXD027171 | iProX
Project description:Germinal centre (GC) B cells proliferate at some of the highest rates of any mammalian cell. Yet the metabolic processes which enable this are poorly understood. We performed integrated metabolomic and transcriptomic profiling of GC B cells, and found that asparagine metabolism is highly upregulated. Asparagine is conditionally essential to B cells, and its synthetic enzyme, asparagine synthetase (ASNS) is markedly upregulated following their activation, through the integrated stress response sensor general control non-derepressible 2 (GCN2). When Asns is deleted, B cell survival in low asparagine conditions is severely impaired. Using stable isotope tracing, we found that metabolic adaptation to the absence of asparagine requires ASNS, and that the synthesis of nucleotides is particularly sensitive to asparagine deprivation. Conditional deletion of Asns in B cells selectively impairs GC formation, associated with a reduction in RNA synthesis rates. Finally, removal of environmental asparagine by asparaginase was found to also severely compromise the GC reaction.
2024-04-03 | GSE228845 | GEO
Project description:Autophagy is a highly conserved self-digestion process, essential to maintain homeostasis and viability in response to nutrient starvation. Although the components of autophagy in the cytoplasm have been well-studied, molecular basis for the epigenetic regulation of autophagy is poorly understood. Here, we identify histone arginine methyltransferase CARM1 as a critical component of autophagy. We found that nutrient starvation increased CARM1 protein level and subsequently histone H3R17 dimethylation. Genome-wide analyses reveal that CARM1 exerts transcriptional coactivator function on autophagy-related genes and lysosomal genes through TFEB. Our findings demonstrate a previously unrecognized role of CARM1-dependent histone arginine methylation as a critical nuclear event of autophagy.
2016-06-17 | GSE72901 | GEO
Project description:Gene expression profiling of leukemia cells following asparagine depletion
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Project description:Periodic starvation of animals induces large shifts in metabolism, but may also influence many other cellular systems and can lead to adaption to prolonged starvation conditions. To date, there is limited understanding of how starvation affects gene expression, particularly at the protein level. Here, we have used mass spectrometry‐based quantitative proteomics to identify global changes in the C. elegans proteome due to acute starvation of young adult animals. Measuring changes in abundance of up to 7,000 proteins, we show that acute starvation rapidly alters the levels of hundreds of proteins, many involved in central metabolic pathways, highlighting key regulatory responses. Surprisingly, we also detect changes in the abundance of chromatin‐associated proteins including specific linker histones, histone variants and histone post‐translational modifications associated with the epigenetic control of gene expression. A null mutant for one of these proteins, the histone H3.3 variant HIS‐71, identified a subset of proteins whose abundance no longer varied in response to starvation. This mutant also displayed defects in starvation stress resistance and showed a reduced adult lifespan. To maximise community access to these data, they are presented in an online searchable database, the Encyclopedia of Proteome Dynamics (http://www.peptracker.com/epd/).
2015-06-17 | PXD001723 | Pride
Project description:Amino acid hydroxylation is a common post-translational modification, which generally regulates protein interactions or adds a functional group that can be further modified. Such hydroxylation is currently considered irreversible, necessitating the degradation and re-synthesis of the entire protein to reset the modification. Here we present evidence that the cellular machinery can reverse FIH-mediated asparagine hydroxylation on intact proteins. These data suggest that asparagine hydroxylation is a flexible and dynamic post-translational modification akin to modifications involved in regulating signalling networks, such as phosphorylation, methylation and ubiquitylation.
2020-03-23 | PXD013116 | Pride
Project description:Single - cell profiling of patient tumours and of mouse models is revealing that many cancers are constituted of communities of genetically and phenotypically distinct clonal lineages 1 - 12. A functional model of breast cancer heterogeneity revealed that clonal sub - populations proficient at generating circulating tumour cells were not equally capable of forming metastases at secondary sites 13. A combination of differential expression and focused in vitro and in vivo RNAi screens revealed candidate drivers of metastasis discriminating these clones, which were then evaluated in gene expression datasets from breast cancer patients. Among these, Asparagine Synthetase (Asns) expression in a patient's primary tumour was most strongly correlated with later metastatic relapse. Silencing of Asns reduced both metastatic potential in vivo and invasive potential in vitro. Conversely, increasing the availability of extracellular asparagine increased the invasive potential of mouse and human breast cancer cells, and enforced Asns expression promoted metastasis. Decreasing asparagine availability in mice by treatment with L-asparaginase or even by dietary restriction strongly reduced metastasis from orthotopic tumours. Asparagine availability varies betwe en tissues, potentially explaining selective effects on particular steps of tumor progression. Asparagine limitation reduced the production of proteins that promote the epithelial to mesenchymal transition, providing one potential mechanism for how the availability of a single amino acid could regulate metastatic progression.
2018-02-08 | GSE107109 | GEO
Project description:To identify sites of methylated residues, histone derived from HEK293T was analyzed by MALDI-TOF/MS.
2023-06-08 | PXD042812 | JPOST Repository