Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression analysis upon mtDNA depletion [microarray]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE99834 | GEO | 2018/03/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

ChIP-seq analysis of 143B cells upon mtDNA depletion and metabolic intervention [ChIP-Seq 2]

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

Gene expression analysis upon mtDNA depletion [ChIP-seq]

2018-03-21 | GSE100133 | GEO

Gene expression analysis upon mtDNA depletion [RNA-seq]

2018-03-21 | GSE100132 | GEO

Gene expression analysis upon mtDNA depletion [methylation]

2018-03-21 | GSE100249 | GEO

Glucose Starvation Induces a Switch in the Histone Acetylome for Activation of Gluconeogenic and Fat Metabolism Genes [RNA-seq]

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

Glucose Starvation Induces a Switch in the Histone Acetylome for Activation of Gluconeogenic and Fat Metabolism Genes [ChIP-seq]

2022-01-06 | GSE178159 | GEO

Cytosolic acetyl-CoA promotes histone acetylation predominantly at H3K27 in Arabidopsis

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

Acetyl-CoA production by Mediator-bound 2-ketoacid dehydrogenases boosts de novo histone acetylation and is regulated by nitric oxide [Med1_Chipseq]

Project description:Histone modifying enzymes depend on the availability of cofactors, with acetyl-CoA being required for histone acetyltransferase (HAT) activity. The discovery that mitochondrial acyl-CoA producing enzymes are also delivered to the nucleus suggests that high concentrations of metabolites generated locally may impact acetylation of histones and other nuclear substrates and eventually control gene regulation. Here we show that 2-ketoacid dehydrogenases were stably associated with the Mediator complex in macrophages, thus providing a local supply of acetyl-CoA and increasing the generation of hyper-acetylated histone tails. Nitric oxide (NO), which is produced in large amounts in LPS-stimulated macrophages, inhibited both the activity of 2-ketoacid dehydrogenases and their association with Mediator. Consequently, NO reduced de novo histone acetylation at genomic regions with high acetyl-CoA deposition rates. Our findings indicate that a local supply of acetyl-CoA generated by Mediator-bound 2-ketoacid dehydrogenases is required to maximize acetylation of histone tails at sites of elevated HAT activity. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for the Mediator subunit Med1 (cat.no. A300-793A, Bethyl)

2024-11-19 | GSE227963 | GEO

Acetyl-CoA production by Mediator-bound 2-ketoacid dehydrogenases boosts de novo histone acetylation and is regulated by nitric oxide [Chrom_RNAseq_iNOS1400W]

2024-11-19 | GSE245445 | GEO

Acetyl-CoA production by Mediator-bound 2-ketoacid dehydrogenases boosts de novo histone acetylation and is regulated by nitric oxide [Chipseq_panAc_spikein]

2024-11-19 | GSE245444 | GEO