Sodium arsenite effects on DNA methylation in zebrafish embryos.
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE90735 | GEO | 2017/10/19
SECONDARY ACCESSION(S): PRJNA355643
REPOSITORIES: GEO
Similar Datasets
Project description:Arsenic (As) exposure is a significant worldwide environmental health concern. Low dose, chronic arsenic exposure has been associated with higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. While arsenic-induced biological changes play a role in disease pathology, little is known about the dynamic cellular changes due to arsenic exposure and withdrawal. In these studies, we seek to understand the molecular mechanisms behind the biological changes induced by chronic low doses of arsenic exposure. We used a comprehensive approach involving chromatin structural studies and mRNA microarray analyses to determine how chromatin structure and gene expression patterns change in response to chronic low dose arsenic exposure and its subsequent withdrawal. Our results show that cells exposed to low doses of sodium arsenite have distinct temporal and coordinated chromatin, gene expression and miRNA changes that are consistent with differentiation and activation of multiple biochemical pathways. Most of these temporal patterns in gene expression are reversed when arsenic was withdrawn. However, some of the gene expression patterns remained altered, plausibly as a result of an adaptive response by these cells. Additionally, these gene expression patterns correlated with changes in chromatin structure, further solidifying the role of chromatin structure in gene regulatory changes due to arsenite exposure. Lastly, we show that arsenite exposure influences gene regulation both at the transcription initiation as well as at the splicing level. Thus our results suggest that general patterns of alternative splicing, as well as expression of particular gene regulators, can be indicative of arsenite-induced cell transformation. A total of eight (8) samples with two biological replicates under four separate conditions: wild-type treated with deionized H2O for 36 days (NT); chronic low-dose arsenic exposure of 1 uM of sodium arsenite (iAs-T) for 36 days; chronic arsenic exposure of 1 uM of sodium arsenite for 26 days followed by removal of sodium arsenite for 10 days, measured at day 36 (iAs-Rev); and chronic arsenic exposure of 1 uM of sodium arsenite for 26 days, followed by removal of sodium arsenite exposure for 10 days, followed by 1 uM of chronic sodium arsenite exposure for 10 days (measured at day 46) (iAs-Rev-T).
2015-05-05 | E-GEOD-60760 | biostudies-arrayexpress
Project description:Arsenic (As) exposure is a significant worldwide environmental health concern. Low dose, chronic arsenic exposure has been associated with higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. While arsenic-induced biological changes play a role in disease pathology, little is known about the dynamic cellular changes due to arsenic exposure and withdrawal. In these studies, we seek to understand the molecular mechanisms behind the biological changes induced by chronic low doses of arsenic exposure. We used a comprehensive approach involving chromatin structural studies and mRNA microarray analyses to determine how chromatin structure and gene expression patterns change in response to chronic low dose arsenic exposure and its subsequent withdrawal. Our results show that cells exposed to low doses of sodium arsenite have distinct temporal and coordinated chromatin, gene expression and miRNA changes that are consistent with differentiation and activation of multiple biochemical pathways. Most of these temporal patterns in gene expression are reversed when arsenic was withdrawn. However, some of the gene expression patterns remained altered, plausibly as a result of an adaptive response by these cells. Additionally, these gene expression patterns correlated with changes in chromatin structure, further solidifying the role of chromatin structure in gene regulatory changes due to arsenite exposure. Lastly, we show that arsenite exposure influences gene regulation both at the transcription initiation as well as at the splicing level. Thus our results suggest that general patterns of alternative splicing, as well as expression of particular gene regulators, can be indicative of arsenite-induced cell transformation.
2015-05-05 | GSE60760 | GEO
Project description:Arsenic is methylated during its metabolism, thereby depleting the intracellular methyl donor S-adenosyl-methionine, which may lead to disturbances in DNA methylation patterns Cells were exposed to sodium arsenite (NaAsO2, Sigma) at concentrations of 0.08 M-BM-5M, 0.4 M-BM-5M and 2 M-BM-5M for 1, 2 and 8 weeks. A549 arsenic dose time response study.
2014-09-17 | E-GEOD-44173 | biostudies-arrayexpress
Project description:Arsenic is methylated during its metabolism, thereby depleting the intracellular methyl donor S-adenosyl-methionine, which may lead to disturbances in DNA methylation patterns which could lead to altered gene expression Cells were exposed to sodium arsenite (NaAsO2, Sigma) at concentrations of 0.08 M-BM-5M, 0.4 M-BM-5M and 2 M-BM-5M for 1, 2 and 8 weeks.
2014-09-17 | E-GEOD-44169 | biostudies-arrayexpress
Project description:Arsenic contamination in food and ground water constitutes a public health concern to more than 100 million people worldwide. Individuals chronically exposed to arsenic through drinking and ingestion exhibit a higher risk in developing cancers and cardiovascular diseases. Nevertheless, the underlying mechanisms of arsenic toxicity are not fully understood. Arsenite is known to bind to and deactivate RING finger E3 ubiquitin ligases; thus, we reason that a systematic interrogation about how arsenite exposure modulates global protein ubiquitination may reveal novel molecular targets for arsenic toxicity. By employing liquid chromatography-tandem mass spectrometry, in combination with stable isotope labeling by amino acids in cell culture (SILAC) and immunoprecipitation of di-glycine-conjugated lysine-containing tryptic peptides, we assessed the alterations in protein ubiquitination in GM00637 human skin fibroblast cells upon arsenite exposure at the entire proteome level. We observed that arsenite exposure led to altered ubiquitination of many proteins, where the alterations in a large majority of ubiquitination events are negatively correlated with changes in expression of the corresponding proteins, suggesting their modulation by the ubiquitin-proteasomal pathway. Moreover, we observed that arsenite exposure confers diminished ubiquitination of a rate-limiting enzyme in cholesterol biosynthesis, HMGCR, at Lys248. In addition, we revealed that TRC8 is the major E3 ubiquitin ligase for HMGCR ubiquitination in HEK293T cells, and the arsenite-induced diminution of HMGCR ubiquitination is abrogated with depletion of TRC8. In summary, we systematically characterized arsenite-induced perturbations in ubiquitinated proteome in human cells, and found that the arsenite-elicited diminution of HMGCR ubiquitination involves TRC8.
2023-10-24 | PXD035401 | Pride
Project description:Arsenic is a potent environmental toxin and a cause of numerous health problems. Most studies have assumed that arsenic-induced changes in mRNA levels result from effects on gene transcription. The influence of arsenic on post-transcriptional regulation, another important locus of gene expression control, has remained largely unexplored. To evaluate the prevalence of changes in mRNA stability in response to arsenic in human fibroblasts, we used microarray analyses to determine changes in steady state mRNA levels, and their decay rates, following 24 hour exposure to non-cytotoxic concentrations of sodium arsenite (1 µM). We conclude that arsenite modification of mRNA stability is relatively uncommon, but in some instances can result in significant changes in gene expression.
2015-04-15 | GSE57051 | GEO
Project description:Arsenic is a potent environmental toxin and a cause of numerous health problems. Most studies have assumed that arsenic-induced changes in mRNA levels result from effects on gene transcription. The influence of arsenic on post-transcriptional regulation, another important locus of gene expression control, has remained largely unexplored. To evaluate the prevalence of changes in mRNA stability in response to arsenic in human fibroblasts, we used microarray analyses to determine changes in steady state mRNA levels, and their decay rates, following 24 hour exposure to non-cytotoxic concentrations of sodium arsenite (1 µM). We conclude that arsenite modification of mRNA stability is relatively uncommon, but in some instances can result in significant changes in gene expression. Human BJ diploid foreskin fibroblasts were used in the study. The decay rates of transcripts were determined using actinomycin D to stop transcription after sodium arsenite or water treatment for 24 h. Actinomycin D was added into the culture medium at a final concentration of 5 µg/ml, and treated cells were then harvested at 0, 1, 2, 3 and 4 h for RNA extraction.
2015-04-15 | E-GEOD-57051 | biostudies-arrayexpress
Project description:Both epidemiological investigations and animal studies have linked arsenic-contaminated water to cancers, in- cluding skin, liver and lung cancers. Besides genotoxicity, arsenic exposure-related pathogenesis of disease is widely considered through epigenetic mechanisms; however, the underlying mechanism remains to be deter- mined. Herein we explore the initial epigenetic changes via acute sodium arsenite (As) exposures of mouse em- bryonic fibroblast (MEF) cells and histone H3K79 methyltransferase Dot1L knockout (Dot1L− /−) MEF cells. Our RNA-seq and Western blot data demonstrated that, in both cell lines, acute As exposure abolished histone acetyl- transferase p300 at the RNA level and subsequent protein level. Consequently, p300-specific main target histone H3K27ac, a marker separating active from poised enhancers, decreased dramatically as validated by both West- ern blot and ChIP-qPCR/seq analyses. Concomitantly, H3K4me1 as another well-known marker for enhancers also showed significant decreases, suggesting an underappreciated crosstalk between H3K4me1 and H3K27ac involved in As exposure. Significantly, As exposure-reduced H3K27ac and H3K4me1 inhibited the expression of genes including EP300 itself and Kruppel Like Factor 4(Klf4) that both are tumor suppressor genes. Collectively, our investigations identified p300 as an internal bridging factor within cells to sense external environmental As exposure to alter chromatin, thereby changing gene transcription for disease pathogenesis.
2020-12-10 | GSE118827 | GEO
Project description:This study was carried out to compare the changes in gene expression in 5 dpf zebrafish larval livers in response to mutation of the arsenic methylation gene (as3mt) - 8 bp deletion in exon 3 with and without 1 mM sodium arsenite treatment (96-120 hpf)
2023-05-01 | GSE228752 | GEO
Project description:Talemi2014 - Arsenic toxicity and
detoxification mechanisms in yeast
The model implements arsenite (AsIII)
transport regulation, its distribution within main cellular AsIII
pools and detoxification. The intracellular As pools considered are
free AsIII (AsIIIin), protein-bound AsIII (AsIIIprot), glutathione
conjugated AsIII (AsGS3) and vacuolar sequestered AsIII (vAsGS3).
This model is described in the article:
Mathematical modelling of
arsenic transport, distribution and detoxification processes in
yeast.
Talemi SR, Jacobson T, Garla V,
Navarrete C, Wagner A, Tamás MJ, Schaber J.
Mol. Microbiol. 2014 Jun; 92(6):
1343-1356
Abstract:
Arsenic has a dual role as causative and curative agent of
human disease. Therefore, there is considerable interest in
elucidating arsenic toxicity and detoxification mechanisms. By
an ensemble modelling approach, we identified a best
parsimonious mathematical model which recapitulates and
predicts intracellular arsenic dynamics for different
conditions and mutants, thereby providing novel insights into
arsenic toxicity and detoxification mechanisms in yeast, which
could partly be confirmed experimentally by dedicated
experiments. Specifically, our analyses suggest that: (i)
arsenic is mainly protein-bound during short-term (acute)
exposure, whereas glutathione-conjugated arsenic dominates
during long-term (chronic) exposure, (ii) arsenic is not stably
retained, but can leave the vacuole via an export mechanism,
and (iii) Fps1 is controlled by Hog1-dependent and
Hog1-independent mechanisms during arsenite stress. Our results
challenge glutathione depletion as a key mechanism for arsenic
toxicity and instead suggest that (iv) increased glutathione
biosynthesis protects the proteome against the damaging effects
of arsenic and that (v) widespread protein inactivation
contributes to the toxicity of this metalloid. Our work in
yeast may prove useful to elucidate similar mechanisms in
higher eukaryotes and have implications for the use of arsenic
in medical therapy.
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2014-09-04 | BIOMD0000000547 | BioModels