Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epigenetic changes of the thioredoxin system in the tx-j mouse model and in patients with Wilson disease

ABSTRACT: Epigenetic changes of the thioredoxin system in the tx-j mouse model and in patients with Wilson disease

PROVIDER: PRJNA482607 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR7586690.fastq.gz	Fastqsanger.gz
	SRR7586700.fastq.gz	Fastqsanger.gz
	SRR7586691.fastq.gz	Fastqsanger.gz
	SRR7586701.fastq.gz	Fastqsanger.gz
	SRR7586692.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 16

Similar Datasets

Epigenetic changes of the thioredoxin system in the tx-j mouse model and in patients with Wilson disease

Project description:Wilson disease (WD) is caused by mutations in the copper transporter ATP7B, leading to copper accumulation in the liver and brain. Excess copper inhibits S-adenosyl-L-homocysteine hydrolase, leading to variable WD phenotypes from widespread alterations in DNA methylation and gene expression. Previously, we demonstrated that maternal choline supplementation in the Jackson toxic milk (tx-j) mouse model of WD corrected higher thioredoxin 1 transcript levels in fetal liver. Here, we investigated the effect of maternal choline supplementation on genome-wide DNA methylation patterns in tx-j fetal liver by whole-genome bisulfite sequencing (WGBS). Tx-j Atp7b genotype-dependent differences in DNA methylation were corrected by choline for genes including, but not exclusive to, oxidative stress pathways. To examine phenotypic effects of postnatal choline supplementation, tx-j mice were randomized to one of six treatment groups: with or without maternal and/or continued choline supplementation, and with or without copper chelation with penicillamine (PCA) treatment. Hepatic transcript levels of thioredoxin 1 and peroxiredoxin 1 were significantly higher in mice receiving maternal and continued choline with or without PCA treatment compared to untreated mice. A comparison of WGBS of human WD liver compared to tx-j mouse liver demonstrated a significant overlap of differentially-methylated genes associated with ATP7B deficiency. Further, eight genes in the thioredoxin pathway were differentially methylated in human WD liver samples. In summary, Atp7b deficiency and choline supplementation have a genome-wide impact, including on thioredoxin system-related genes, in tx-j mice. These findings could explain the variability of WD phenotype and suggest new complementary treatment options for WD.

2018-07-25 | GSE117592 | GEO

Epigenetic changes of the thioredoxin system in the tx-j mouse model and in patients with Wilson disease.

Project description:Wilson disease (WD) is caused by mutations in the copper transporter ATP7B, leading to copper accumulation in the liver and brain. Excess copper inhibits S-adenosyl-L-homocysteine hydrolase, leading to variable WD phenotypes from widespread alterations in DNA methylation and gene expression. Previously, we demonstrated that maternal choline supplementation in the Jackson toxic milk (tx-j) mouse model of WD corrected higher thioredoxin 1 (TNX1) transcript levels in fetal liver. Here, we investigated the effect of maternal choline supplementation on genome-wide DNA methylation patterns in tx-j fetal liver by whole-genome bisulfite sequencing (WGBS). Tx-j Atp7b genotype-dependent differences in DNA methylation were corrected by choline for genes including, but not exclusive to, oxidative stress pathways. To examine phenotypic effects of postnatal choline supplementation, tx-j mice were randomized to one of six treatment groups: with or without maternal and/or continued choline supplementation, and with or without copper chelation with penicillamine (PCA) treatment. Hepatic transcript levels of TXN1 and peroxiredoxin 1 (Prdx1) were significantly higher in mice receiving maternal and continued choline with or without PCA treatment compared to untreated mice. A WGBS comparison of human WD liver and tx-j mouse liver demonstrated a significant overlap of differentially methylated genes associated with ATP7B deficiency. Further, eight genes in the thioredoxin (TXN) pathway were differentially methylated in human WD liver samples. In summary, Atp7b deficiency and choline supplementation have a genome-wide impact, including on TXN system-related genes, in tx-j mice. These findings could explain the variability of WD phenotype and suggest new complementary treatment options for WD.

| S-EPMC6216211 | biostudies-literature

Effects of redox modulation by inhibition of Thioredoxin reductase on radiosensitivity and gene expression

2010-12-03 | GSE25814 | GEO

The thioredoxin-1 system is essential for fueling DNA synthesis during T cell metabolic reprogramming and proliferation

Project description:The thioredoxin-1 (Trx1) system is a key player of the cellular redox balance and a sensor of energy and glucose metabolism. Here we report critical c-Myc-dependent activation of the Trx1 system during glucose-driven T cell expansion during development and immune responses but endogenous Trx1-repression during quiescence. Thioredoxin-reductase-1 (Txnrd1)-deletion in CD4-CD8- thymocytes prevented their expansion, while deletion in CD4+CD8+ thymocytes did not affect further maturation and peripheral homeostasis of T-cells. Moreover, B cell development was Txnrd1-independent. Txnrd1 was critical for expansion of activated T cells. Unbiased metabolomics revealed that Txnrd1 is necessary for donating reducing equivalent to ribonucleotide reductase (RNR) at the last step of nucleotide biosynthesis. Impaired availability of 2’-deoxyribonucleotides induced the DNA damage response and cell cycle arrest of Txnrd1-deficient T cells. These results uncover a pivotal role of the Trx1 system in metabolic reprograming of thymic and peripheral T cells and provide a rationale for targeting of Txnrd1 in T-cell leukemia.

2018-03-15 | GSE107090 | GEO

Shifted Metabolic Bias in Livers of Mice Lacking Hepatocytic Thioredoxin Reductase-1 Protects Against Acetaminophen Toxicity

Project description:Genetic disruption of thioredoxin reductase 1 protects against acetaminophen (APAP) toxicity. To determine the role of the thioredoxin system on xenobiotic metabolism we challeneged wildtype and txnrd1liver-null mice with acetaminophen.

2013-06-08 | GSE37874 | GEO

Effects of redox modulation by inhibition of Thioredoxin reductase on radiosensitivity and gene expression

Project description:The involvement the thioredoxin system in radiation resistance was investigated in human lung cancer cells by a combination of ionizing radiation and specific thioredoxin reductase-inhibition by a phosphine gold compound. Gene expression profiles (Human Gene 1.0 ST) of lung cancer cells subjected to ionizing radiation and/or inhibition of thioredoxin reductase were studied. Data analyses were performed using the Affymetrix GeneChip Operating Software (GCOS) Version 1.4.

2010-12-03 | E-GEOD-25814 | biostudies-arrayexpress

Wilson disease: intersecting DNA methylation and histone acetylation mechanisms affect gene expression regulation in a mouse model of hepatic copper accumulation [ChIP-Seq]

Project description:Prior investigations of DNA methylation differences in WD liver and blood and in a WD mouse model revealed an epigenetic signature of WD that included the histone deacetylase, HDAC5. To test the hypothesis that histone deacetylation and acetylation might be altered with respect to copper overload and aberrant DNA methylation in WD, we used the Jackson Laboratory toxic milk model (tx-j) of WD to study the involvement of Class IIa histone deacetylases (HDAC4 and HDAC5) and histone acetylation (H3K9ac and H3K27ac), and the effects of copper chelator D-penicillamine (PCA) and/or methyl group donor choline on histone modification. Next, we related acetylation profiles of H3K27ac to gene expression changes in wilson disease by ChIP and RNA-seq.

2021-07-09 | GSE168971 | GEO

Wilson disease: intersecting DNA methylation and histone acetylation mechanisms affect gene expression regulation in a mouse model of hepatic copper accumulation [RNA-Seq]

2021-07-09 | GSE168833 | GEO

Transcription profiling of mutations in the yeast TRR1 gene encoding thioredoxin reductase

Project description:The Saccharomyces cerevisiae Yap1p transcription factor is required for the H2O2-dependent activation of many antioxidant genes including the TRX2 gene encoding thioredoxin 2. To identify factors that regulate Yap1p activity, we carried out a genetic screen for mutants that show elevated expression of a TRX2-HIS3 fusion in the absence of H2O2. Two independent mutants isolated in this screen carried mutations in the TRR1 gene encoding thioredoxin reductase. Northern blot and whole-genome expression analysis revealed that the basal expression of most Yap1p targets and many other H2O2-inducible genes is elevated in Deltatrr1 mutants in the absence of external stress. In Deltatrr1 mutants treated with H2O2, the Yap1p targets, as well as genes comprising a general environmental stress response and genes encoding protein-folding chaperones, are hyperinduced. However, despite the elevated expression of genes encoding antioxidant enzymes, Deltatrr1 mutants are extremely sensitive to H2O2. The results suggest that cells lacking thioredoxin reductase have diminished capacity to detoxify oxidants and/or to repair oxidative stress-induced damage and that the thioredoxin system is involved in the redox regulation of Yap1p transcriptional activity.

2005-06-30 | E-SMDB-2716 | biostudies-arrayexpress

Karenia brevis isolate:Wilson

Project description:Karenia brevis isolate:Wilson Transcriptome or Gene expression

| PRJNA342844 | ENA