Metabolic dependencies of metastasis-initiating cells in breast cancer [ChIP-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE236223 | GEO | 2023/09/20
REPOSITORIES: GEO
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Project description:We found acetyl-CoA levels increase when cells are committed to growth. We also found 3 components of the SAGA complex, Spt7p, Sgf73p and Ada3p as well as histones are dynamically acetylated in tune with the acetyl-CoA levels. ChIP-seq study reveals SAGA and H3K9ac predominantly occupy growth genes at the OX growth phase of the yeast metabolic cycle indicating acetyl-CoA levels may drive growth gene transcription program through acetylation of these proteins. Examination of H3K9ac and SAGA binding over two timepoints using H3 and Input as controls
2011-05-19 | E-GEOD-28734 | biostudies-arrayexpress
Project description:Liver tumors had high levels of histone acetylation. Nrf2 knockout mice developed fewer tumors than Nrf2 wild-type mice. The mechanistic study found that Nrf2 knockout reduced the generation of acetyl CoA from impaired glycolysis, TCA cycle, and fatty acid metabolism. Acetyl CoA is the substrate for protein acetylation including histone acetylation. Here we determined the genome-wide distribution of AcH3K27. We found that Nrf2 through regulating acetyl CoA production affects histone acetylation (AcH3K27) to modulate the expression of genes, whose products were involved in the glycolysis, TCA cycle, fatty acid metabolism, and oncogenic Myc/mTor signaling. Our findings supported an Nrf2-integrated metabolic, epigenetic and oncogenic signaling in driving liver tumor development.
2023-03-20 | GSE227068 | GEO
Project description:We found acetyl-CoA levels increase when cells are committed to growth. We also found 3 components of the SAGA complex, Spt7p, Sgf73p and Ada3p as well as histones are dynamically acetylated in tune with the acetyl-CoA levels. ChIP-seq study reveals SAGA and H3K9ac predominantly occupy growth genes at the OX growth phase of the yeast metabolic cycle indicating acetyl-CoA levels may drive growth gene transcription program through acetylation of these proteins.
2011-05-19 | GSE28734 | GEO
Project description:Formation of myelin by Schwann cells is tightly coupled to nervous system development and is important for neuronal function and long-term maintenance. Perturbation of myelin causes a number of specific disorders that are among the most prevalent diseases affecting the nervous system. Schwann cells synthesize myelin lipids de novo rather than relying on uptake of circulating lipids, and the metabolic sources of myelin formation and maintenance in vivo remain unresolved. One of these questions is how a central metabolite in myelin formation, Acetyl CoA, is generated in myelinating cells. Acetyl CoA-generating pathways are induced at the level of gene expression to support high demands for lipid synthesis and acetylation reactions. However, recent studies have shown that glucose-derived Acetyl CoA itself is not required for myelination, and the requirements of mitochondrially-derived Acetyl CoA has never been tested for myelination in vivo. Several older labeling studies have demonstrated the possibility that cytosolic Acetyl CoA-generating pathways from acetate/ketone bodies satisfy the high demands for lipid synthesis and histone acetylation, and we have employed knockout mice to test the required pathways. Intriguingly, metabolic pathways play different role during the postnatal synthesis of myelin lipids in the postnatal period compared to myelin maintenance postweaning.
2024-02-01 | GSE252209 | GEO
Project description:Acetyl-Coenzyme A (acetyl-CoA) is a central metabolite and the acetyl source for protein acetylation, particularly histone acetylation that promotes gene expression. However, the effect of acetyl-CoA levels on histone acetylation status in plants remains unknown. Here, we show that malfunctioned cytosolic acetyl-CoA carboxylase1 (ACC1) in Arabidopsis leads to elevated levels of acetyl-CoA and promotes histone hyperacetylation predominantly at lysine 27 of histone H3 (H3K27). The increase of H3K27 acetylation (H3K27ac) is dependent on ATP-citrate lyase which cleaves citrate to acetyl-CoA in the cytoplasm, and requires histone acetyltransferase GCN5. A comprehensive analysis of the transcriptome and metabolome in combination with the genome-wide H3K27ac profiles of acc1 mutants, demonstrate the dynamic changes of H3K27ac, gene transcripts and metabolites occurring in the cell by the increased levels of acetyl-CoA. This study suggests that H3K27ac is an important link between cytosolic acetyl-CoA level and gene expression in response to the dynamic metabolic environments in plants.
2017-09-25 | GSE79524 | GEO
Project description:Metabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and directchum regulator of histone acetylation in neurons and of long-term mammalian memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory. These results reveal a unique connection between cellular metabolism and neural plasticity, and establish a link between generation of acetyl-CoA and neuronal chromatin regulation. Genome-wide examination of histone H3 and H4 acetylation, as well as ACSS2 binding, in undifferentiated CAD cells and differentiated CAD neurons; background adjusted by H3 ChIP or Input.
2017-05-01 | E-GEOD-76850 | biostudies-arrayexpress
Project description:Histone acetylation is important for the transcriptional regulation in the ethylene response and the nuclear metabolic production of acetyl coenzyme A (acetyl-CoA) plays key roles in histone acetylation. But how the nucleus produces acetyl-CoA for histone acetylation and transcription regulation in the ethylene response is completely unknown. Here we show that functional pyruvate dehydrogenase complex (PDC) translocates from the mitochondria to the nucleus in response to ethylene, generating nuclear acetyl CoA from pyruvate to regulate EIN2-directed histone acetylation and transcription in the target genes. It has been reported that the dephosphorylated E1 subunit of the PDC complex is required for the PDC activity, we examined the phosphorylation status change of E1 in the nucleus in response to ethylene. The MS data shows quantitative phosphorylation differences between cytosolic and nuclear fraction supporting the dephosphorylation of E1 upon ethylene treatment.
2024-06-25 | PXD040689 | Pride
Project description:The goal of the study was to understand whether mitochondrial-driven epigenetic changes regulate gene expression. Mitochondrial metabolism has been implicated in epigenetics but the extent to which this impacts gene expression is unclear. Here we show that loss of mitochondrial DNA (mtDNA) results in locus-specific alterations in histone acetylation, DNA methylation and expression of a subset of genes. Most of these changes are rescued by restoring mitochondrial electron transport in a way that maintains the oxidative tricarboxylic acid cycle, but not reactive oxygen species or ATP production, or by modulating the mitochondrial pool of acetyl-CoA. Changes in acetyl-CoA and histone acetylation precede overt mitochondrial dysfunction and significant changes in gene expression and DNA methylation. This suggests that acetyl-CoA levels signal mitochondrial status to the nucleus. Differentially expressed genes with altered histone marks or DNA methylation regulate amino acid degradation, which likely compensates for the changes in acetyl-CoA and one carbon metabolism. These have the potential to further affect methylation reactions, redox control and nucleotide levels. These results illustrate the extent to which mitochondria impact cell physiology through epigenetic remodeling.
2019-02-07 | GSE126138 | GEO
Project description:Our studies indicate that glucose and acetate can regulate histone acetylation by altering the acetyl-CoA concentrations in the cell. The purpose of this study was to to determine whether specific gene sets correlated with acetyl-CoA availability. We conclude that 10% of glucose-regulated genes are acetyl-CoA regulated genes (genes suppressed or induced by low glucose and reversed by acetate). Acetate usually regulated gene expression in the same direction as glucose, suggesting that acetyl-CoA is a key mediator of glucose-dependent gene expression. The experiments were performed in quadruplicates for each condition with a total of 12 samples
2014-08-05 | E-GEOD-57488 | biostudies-arrayexpress
Project description:Histone acetylation, a post-translational modification associated with transcriptional activation, is governed by nuclear acetyl-CoA pools that can vary depending on the metabolic state of the cell. The metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is proposed to regulate nuclear acetyl-CoA levels, using local acetate to produce acetyl-CoA that is utilized for histone acetylation. We hypothesize that during gene activation, a local transfer of intact acetate occurs between histones to upregulate transcription via sequential action of epigenetic and metabolic enzymes. Here we present converging lines of evidence in support of this acetate transfer to serve rapid gene induction. Using stable isotope labeling, we detect local transfer of intact acetate between histone acetylation sites both in vitro using purified mammalian enzymes and in vivo using quiescence exit in Saccharomyces cerevisiae as a change-of-state model. We delineate the enzymatic components required for this transfer mechanism, finding that ACSS2, histone deacetylase and histone acetyltransferase enzymes are necessary for efficient acetyl-group transfer in vitro. We show that Acs2, the yeast orthologue of ACSS2, is recruited to the genome during quiescence exit, and observe dynamic changes of histone acetylation in the vicinity of Acs2 peaks in vivo. Strikingly, we find that Acs2 is preferentially associated with the most upregulated growth genes, suggesting that acetyl-group transfer might play an important role in increased gene expression. Overall, our data reveal direct transfer of acetate between histone lysine residues to facilitate rapid transcriptional induction, an exchange that may be critical during metabolic alterations and changes in nutrient availability.
2022-01-21 | GSE189445 | GEO