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Acetylation enhances TET2 function in protecting against abnormal DNA methylation during oxidative stress

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE81428 | GEO | 2016/12/31

SECONDARY ACCESSION(S): PRJNA321516

REPOSITORIES: GEO

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Similar Datasets

Acetylation Enhances TET2 Function in Protecting against Abnormal DNA Methylation during Oxidative Stress.

Project description:TET proteins, by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are hypothesized, but not directly shown, to protect promoter CpG islands (CGIs) against abnormal DNA methylation (DNAm) in cancer. We define such a protective role linked to DNA damage from oxidative stress (OS) known to induce this abnormality. TET2 removes aberrant DNAm during OS through interacting with DNA methyltransferases (DNMTs) in a "Yin-Yang" complex targeted to chromatin and enhanced by p300 mediated TET2 acetylation. Abnormal gains of DNAm and 5hmC occur simultaneously in OS, and knocking down TET2 dynamically alters this balance by enhancing 5mC and reducing 5hmC. TET2 reduction results in hypermethylation of promoter CGIs and enhancers in loci largely overlapping with those induced by OS. Thus, TET2 indeed may protect against abnormal, cancer DNAm in a manner linked to DNA damage.

| S-EPMC5260804 | biostudies-literature

Acetylation enhances TET2 function in protecting against abnormal DNA methylation during oxidative stress [A2780 TET2 KO - methylation]

Project description:Genome wide DNA methylation profiling of A2780 control cells (Scr_1 and Scr_2), and A2780 TET2 KO clones (KO1.1, KO1.36, and KO2.32). The Illumina’s Infinium Human Methylation450 Beadchip Kit (WG-314-1001) was used to obtain DNA methylation profiles across approximately 450,000 CpGs.

2016-12-31 | GSE83751 | GEO

Acetylation enhances TET2 function in protecting against abnormal DNA methylation during oxidative stress [gene expression]

Project description:Transcriptional profiling of A2780 cells with genetic TET2 knockout, generated by CRISPR. The aim was to identify genes affected by TET2 KO. Three individual KO clones were profiled. Control cells were cells that infected with control sgRNA.

2016-12-31 | GSE79808 | GEO

Acetylation enhances TET2 function in protecting against abnormal DNA methylation during oxidative stress [shTET2 - H2O2 - methylation]

Project description:Genome wide DNA methylation profilings (Bisulfite (BS), or oxidative bisulfite (oxBS)) were done for A2780 cells 1) infected with control virus, no H2O2 (Scr_mock) treatment, 2) infected with control virus with H2O2 treatment (30 min plus 2.5 h resting) (Scr_H2O2), and 3) infected with shTET2 virus, with H2O2 treatment (30 min plus 2.5 h resting) (shTET2_H2O2). Each genomic DNA was splitted equally to two aliquots. One aliquote was subjected to oxidation (oxBS) and one to mock oxidation (BS) prior to bisulfite treatment (CEGX protocol). The Illumina’s Infinium Human Methylation450 Beadchip Kit (WG-314-1001) was used to obtain DNA methylation profiles across approximately 450,000 CpGs. 5hmC levels were calculated by subtracting oxBS values from BS values.

2016-12-31 | GSE83750 | GEO

Acetylation enhances TET2 function in protecting against abnormal DNA methylation during oxidative stress [A2780 damage time points - methylation]

Project description:Genome wide DNA methylation profiling of A2780 cells untreated (mock), treated with H2O2 for 30 min (H2O2 30 min), or treated with H2O2 for 30 min with additional 2.5 hour resting ( H2O2 3h) . The Illumina’s Infinium Human Methylation450 Beadchip Kit (WG-314-1001) was used to obtain DNA methylation profiles across approximately 450,000 CpGs.

2016-12-31 | GSE81426 | GEO

Acetylation enhances TET2 function in protecting against abnormal DNA methylation during oxidative stress [A2780 TET2KD damage 3h - methylation]

Project description:Genome wide DNA methylation profiling of A2780 cells 1) infected with control virus, no H2O2 (Scr_mock), 2) infected with control virus with H2O2 treatment (30 min plus 2.5 h resting) (Scr_H2O2), 3) infected with shTET2 virus, no H2O2 (shTET2_mock), and 4) infected with shTET2 virus, with H2O2 treatment (30 min plus 2.5 h resting) (shTET2_H2O2, two biological replicates). The Illumina’s Infinium Human Methylation450 Beadchip Kit (WG-314-1001) was used to obtain DNA methylation profiles across approximately 450,000 CpGs.

2016-12-31 | GSE81427 | GEO

Acetylation enhances TET2 function in protecting against abnormal DNA methylation during oxidative stress

Project description:Acetylation enhances TET2 function in protecting against abnormal DNA methylation during oxidative stress

| PRJNA321516 | ENA

Nucleoredoxin guards against oxidative stress by protecting antioxidant enzymes.

Project description:Cellular accumulation of reactive oxygen species (ROS) is associated with a wide range of developmental and stress responses. Although cells have evolved to use ROS as signaling molecules, their chemically reactive nature also poses a threat. Antioxidant systems are required to detoxify ROS and prevent cellular damage, but little is known about how these systems manage to function in hostile, ROS-rich environments. Here we show that during oxidative stress in plant cells, the pathogen-inducible oxidoreductase Nucleoredoxin 1 (NRX1) targets enzymes of major hydrogen peroxide (H2O2)-scavenging pathways, including catalases. Mutant nrx1 plants displayed reduced catalase activity and were hypersensitive to oxidative stress. Remarkably, catalase was maintained in a reduced state by substrate-interaction with NRX1, a process necessary for its H2O2-scavenging activity. These data suggest that unexpectedly H2O2-scavenging enzymes experience oxidative distress in ROS-rich environments and require reductive protection from NRX1 for optimal activity.

| S-EPMC5547615 | biostudies-literature

PaCATB, a secreted catalase protecting Podospora anserina against exogenous oxidative stress.

Project description:A differential mass spectrometry analysis of secreted proteins from juvenile and senescent Podospora anserina cultures revealed age-related differences in protein profiles. Among other proteins with decreased abundance in the secretome of senescent cultures a catalase, termed PaCATB, was identified. Genetic modulation of the abundance of PaCATB identified differential effects on the phenotype of the corresponding strains. Deletion of PaCatB resulted in decreased resistance, over-expression in increased resistance against hydrogen peroxide. While the lifespan of the genetically modified strains was found to be unaffected under standard growth conditions, increased exogenous hydrogen peroxide stress in the growth medium markedly reduced the lifespan of the PaCatB deletion strain but extended the lifespan of PaCatB over-expressors. Overall our data identify a component of the secretome of P. anserina as a new effective factor to cope with environmental stress, stress that under natural conditions is constantly applied on organisms and influences aging processes.

| S-EPMC3184978 | biostudies-literature

Nucleoredoxin Guards against Oxidative Stress by Protecting Antioxidant Enzymes

Project description:Target capture by NRX1, NRX1(C58,378S) containing columns versus a control column. Recombinant NRX1 and mutant NRX1(C58,378S) proteins were immobilised on NHS-activated beads. Proteins were extracted from Arabidopsis plants treated for 24hrs with Pseudomonas syringae ES4326 and put through the columns. Proteins were eluted from columns using DTT.

2016-12-18 | MSV000080429 | MassIVE

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