Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD005040
PROVIDER: PRJNA343729 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:From McDonnell et. al. Cell Reports 2016: Cells integrate nutrient sensing and metabolism to coordinate proper cellular responses to a particular nutrient source. For example, glucose drives a gene expression program characterized by activating genes involved in its metabolism, in part, by increasing glucose-derived histone acetylation. Here, we find that lipid-derived acetyl-CoA is a major source of carbon for histone acetylation. Using 13C-carbon tracing combined with acetyl-proteomics, we show that up to 90% of acetylation on certain histone lysines can be derived from fatty acid carbon, even in the presence of excess glucose. By repressing both glucose and glutamine metabolism, fatty acid oxidation reprograms cellular metabolism leading to increased lipid-derived acetyl-CoA. Gene expression profiling of octanoate-treated hepatocytes shows a pattern of upregulated lipid metabolic genes, demonstrating a specific transcriptional response to lipid. These studies expand the landscape of nutrient sensing and uncover how lipids and metabolism are integrated by epigenetic events that control gene expression.
2016-12-22 | PXD005040 | Pride
Project description:We found that lipid-derived acetyl-CoA is a major source of carbon for histone acetylation. Gene expression profiling of octanoate-treated hepatocytes identified a pattern of upregulated lipid metabolic genes, demonstrating a specific transcriptional response to lipid. These studies expand the landscape of nutrient sensing and uncover how lipids and metabolism are integrated by epigenetic events that control gene expression.
2016-09-22 | GSE87156 | GEO
Project description:Histone acetylation involves the transfer of a two-carbon unit to nucleus as embedded in low-concentration metabolites. We find that lactate, a high-concentration metabolic by-product, can be a major carbon source for histone acetylation, through oxidation-dependent metabolism. Both in cells and in purified nucleus, 13C3-lactate carbons are incorporated into histone H4 (maximum incorporation: ~60%). In purified nucleus, this process depends on nucleus-localized lactate dehydrogenase (LDHA), the knockout of which abrogates the incorporation. Heterologous expression of nucleus-localized LDHA rescues the KO effect. Lactate itself increases histone acetylation, whereas inhibition of LDHA reduces the acetylation. In vitro and in vivo settings exhibit different lactate incorporation patterns, suggesting an influence of the microenvironment. Higher nuclear LDHA localization is observed in pancreatic cancer than in normal tissues, showing the disease relevance. Overall, lactate and nuclear LDHA can be major structural and regulatory players in the metabolism-epigenetics axis controlled by cell’s own or environmental status.
2023-11-21 | GSE235471 | GEO
Project description:Histone modifications commonly integrate environmental stimuli to cellular metabolic outputs by affecting gene expression. Many modifications, including some histone acetylation marks, do not always correlate to transcription, thus pointing towards an alternative role of histone modifications as potential metabolic reservoirs. Using an approach that integrates mass spectrometry- based epi-proteomics and metabolomics with stable isotope tracer studies, we demonstrate that elevated lipids in histone acetyltransferase (HAT)-depleted hepatocytes result from carbon atoms flowing from the deacetylation of multi-acetylated histone H4 to fatty acids. Consistent with this, the enhanced lipid synthesis in HAT-depleted hepatocytes is dependent on the activity of histone deacetylases (HDACs) and acetyl-CoA synthetase ACSS2. Furthermore, we show that during diet-induced lipid synthesis there is a reduction of multi-acetylated histone H4 in hepatocytes and in mouse liver. In addition, overexpression of histone acetyltransferases can reverse diet-induced lipogenesis by blocking lipid droplet accumulation and maintaining the levels of multi-acetylated histone H4. This study unveils an additional link between epigenetics and metabolism whereby histone acetylation reservoirs may serve as a carbon source for lipid synthesis.
2024-02-14 | PXD042624 | Pride
Project description:Acetyl-CoA is a key intermediate in metabolism situated at the intersection of many metabolic pathways. The reliance of histone acetylation on acetyl-CoA enables gene expression to be coordinated with metabolic state. Previous studies have linked abundant histone acetylation to activation of genes involved in cell growth or tumorigenesis. However, under glucose starvation, the extent to which histone acetylation is important for gene expression remains poorly understood. Here, we use a yeast starvation model to unravel a dramatic alteration in global occupancy of histone acetylation following carbon starvation. We observe a shift in the location of histone acetylation marks from growth-promoting genes to genes required for gluconeogenesis and fat metabolism. This switch is mediated by both the histone deacetylase Rpd3 and the Gcn5p/SAGA acetyltransferase. Our findings reveal a striking specificity for histone acetylation in promoting pathways that generate acetyl-CoA for oxidation when intracellular acetyl-CoA is limiting .
2022-01-06 | GSE178160 | GEO
Project description:Acetyl-CoA is a key intermediate in metabolism situated at the intersection of many metabolic pathways. The reliance of histone acetylation on acetyl-CoA enables gene expression to be coordinated with metabolic state. Previous studies have linked abundant histone acetylation to activation of genes involved in cell growth or tumorigenesis. However, under glucose starvation, the extent to which histone acetylation is important for gene expression remains poorly understood. Here, we use a yeast starvation model to unravel a dramatic alteration in global occupancy of histone acetylation following carbon starvation. We observe a shift in the location of histone acetylation marks from growth-promoting genes to genes required for gluconeogenesis and fat metabolism. This switch is mediated by both the histone deacetylase Rpd3 and the Gcn5p/SAGA acetyltransferase. Our findings reveal a striking specificity for histone acetylation in promoting pathways that generate acetyl-CoA for oxidation when intracellular acetyl-CoA is limiting .
2022-01-06 | GSE178159 | GEO
Project description:The gut microbiota influences host epigenetics by fermenting dietary fiber into butyrate. Although butyrate could promote histone acetylation by inhibiting histone deacetylases, it may also undergo oxidation to acetyl-CoA, a necessary cofactor for histone acetyltransferases. Here, we find that epithelial cells from germ-free mice harbor a loss of histone H4 acetylation across the genome except at promoter regions. Using stable isotope tracing in vivo with 13C-labeled fiber, we demonstrate that the microbiota supplies carbon for histone acetylation. Subsequent metabolomic profiling revealed hundreds of labeled molecules and supported a microbial contribution to host fatty acid metabolism, which declined in response to colitis and correlated with reduced expression of genes involved in fatty acid oxidation. These results illuminate the flow of carbon from the diet to the host via the microbiota, disruptions to which may affect energy homeostasis in the distal gut and contribute to the development of colitis.
2022-12-12 | GSE179233 | GEO
Project description:Pseudozyma hubeiensis is a basidiomycete yeast that has the highly desirable traits for lignocellulose valorisation of being equally efficient at utilization of glucose and xylose, and capable of their co-utilization. The species has previously mainly been studied for its capacity to produce secreted biosurfactants in the form of mannosylerythritol lipids, but it is also an oleaginous species capable of accumulating high levels of triacylglycerol storage lipids during nutrient starvation. In this study, we aimed to further characterize the oleaginous nature of P. hubeiensis by evaluating metabolism and gene expression responses during storage lipid formation conditions with glucose or xylose as a carbon source.
2023-03-09 | GSE193998 | GEO
Project description:The gut microbiota influences host epigenetics by fermenting dietary fiber into butyrate. Although butyrate could promote histone acetylation by inhibiting histone deacetylases, it may also undergo oxidation to acetyl-CoA, a necessary cofactor for histone acetyltransferases. Here, we find that epithelial cells from germ-free mice harbor a loss of histone H4 acetylation across the genome except at promoter regions. Using stable isotope tracing in vivo with 13C-labeled fiber, we demonstrate that the microbiota supplies carbon for histone acetylation. Subsequent metabolomic profiling revealed hundreds of labeled molecules and supported a microbial contribution to host fatty acid metabolism, which declined in response to colitis and correlated with reduced expression of genes involved in fatty acid oxidation. These results illuminate the flow of carbon from the diet to the host via the microbiota, disruptions to which may affect energy homeostasis in the distal gut and contribute to the development of colitis.
2022-12-11 | PXD026959 | Pride
Project description:Disruptions to iron-sulfur (Fe-S) clusters, essential cofactors for a broad range of proteins, cause widespread cellular defects resulting in human disease. An underappreciated source of damage to Fe-S clusters are cuprous (Cu1+) ions. Since histone H3 enzymatically produces Cu1+ to support copper-dependent functions, we asked whether this activity could become detrimental to Fe-S clusters. Here, we report that histone H3-mediated Cu1+ toxicity is a major determinant of cellular functional pool of Fe-S clusters. Inadequate Fe-S cluster supply, either due to diminished assembly as occurs in Friedreich’s Ataxia or defective distribution, causes severe metabolic and growth defects in S. cerevisiae. Decreasing Cu1+ abundance, through attenuation of histone cupric reductase activity or depletion of total cellular copper, restored Fe-S cluster-dependent metabolism and growth. Our findings reveal a novel interplay between chromatin and mitochondria in Fe-S cluster homeostasis, and a potential pathogenic role for histone enzyme activity and Cu1+ in diseases with Fe-S cluster dysfunction.
2021-10-21 | ST001954 | MetabolomicsWorkbench