Gene expression analysis upon mtDNA depletion
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ABSTRACT:
PROVIDER: PRJNA390778 | ENA |
REPOSITORIES: ENA
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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.
2018-03-21 | GSE100249 | GEO
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.
2018-03-21 | GSE99834 | GEO
Project description:ChIP-seq analysis of 143B cells upon mtDNA depletion and metabolic intervention [ChIP-Seq 2]
| PRJNA521113 | ENA
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.
2018-03-21 | GSE100132 | GEO
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.
2018-03-21 | GSE100133 | GEO
Project description:Genome-wide transcriptional profiles of parental and mtDNA-depleted mouse embryonic fibroblasts. Analysis revealed a downregulation of ChrM genes. Mcl1 knockout mouse embryonic fibroblasts (transformed with SV40 large T antigen) were cultured for 7 days with Ethidium Bromide (100 ng/mL) in DMEM supplemented with Glucose (4.5 g/L), Uridine (50 ug/mL) and Sodium Pyruvate (100 ug/mL). Depletion of mtDNA was assessed by quantitative real-time PCR. Total RNA was isolated and up to 250 ng of total RNA per sample was labelled and hybridized to Illumina Mouse WG6V2 expression BeadChip platform. Three replicate samples were available for each population.
2014-11-03 | E-GEOD-59972 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-03-21 | GSE100134 | GEO
Project description:Effect of depletion of C17orf80 on mtDNA transcription in HEK-293T cells
2023-09-02 | GSE224121 | GEO
Project description:Mitochondria are vital in providing cellular energy via their oxidative phosphorylation system, which requires the coordinated expression of genes encoded by both the nuclear and mitochondrial genomes (mtDNA). Transcription of the circular mammalian mtDNA depends on a single mitochondrial RNA polymerase (POLRMT). Although the transcription initiation process is well understood, it remains highly controversial if POLRMT also serves as the primase for initiation of mtDNA replication. In the nucleus, the RNA polymerases needed for gene expression have no such role. Conditional knockout of Polrmt in heart results in severe mitochondrial dysfunction causing dilated cardiomyopathy in young mice. We further studied the molecular consequences of different expression levels of POLRMT and found that POLRMT is essential for primer synthesis to initiate mtDNA replication in vivo. Furthermore, transcription initiation for primer formation has priority over gene expression. Surprisingly, mitochondrial transcription factor A (TFAM) exists in an mtDNA-free pool in the Polrmt knockout mice. TFAM levels remain unchanged despite strong mtDNA depletion and TFAM is thus protected from degradation of the AAA+ Lon protease in absence of POLRMT. Lastly, mitochondrial transcription elongation factor (TEFM) can compensate for a partial depletion of POLRMT in heterozygous Polrmt knockout mice, indicating a direct regulatory role for this factor in transcription. In conclusion, we present here the first in vivo evidence that POLRMT has a key regulatory role in replication of mammalian mtDNA and is part of a mechanism that provides a switch between RNA primer formation for mtDNA replication and mtDNA expression. Isolated heart mitochondria from three control mice (L/L) and three Polrmt knockout mice (L/L, cre), aged 3-4 weeks, were sequenced and analyzed for differential expression.
2016-08-05 | E-GEOD-83368 | biostudies-arrayexpress
Project description:Analysis of rRNA 2'-O-methylation plasticity upon fibrillarin depletion
| PRJEB43738 | ENA