SABioscience mouse PCR array of the ear tissues of Nickel allergy model
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Naozumi Ishimaru
PROVIDER: E-GEOD-52466 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Histone modifications associated with gene silencing typically mark large contiguous regions of the genome forming repressive chromatin domain structures. Since the repressive domains exist in close proximity to active regions, maintenance of domain structure is critically important. This study shows that nickel, a nonmutagenic carcinogen, can disrupt histone H3 lysine 9 dimethylation (H3K9me2) domain structures genome-wide, resulting in spreading of H3K9me2 marks into the active regions, which is associated with gene silencing. Our results suggest inhibition of DNA binding of the insulator protein CCCTC-binding factor (CTCF) at the H3K9me2 domain boundaries as a potential reason for H3K9me2 domain disruption. These findings have major implications in understanding chromatin dynamics and the consequences of chromatin domain disruption during pathogenesis. Investigations into the genomic landscape of histone modifications in heterochromatic regions have revealed histone H3 lysine 9 dimethylation (H3K9me2) to be important for differentiation and maintaining cell identity. H3K9me2 is associated with gene silencing and is organized into large repressive domains that exist in close proximity to active genes, indicating the importance of maintenance of proper domain structure. Here we show that nickel, a nonmutagenic environmental carcinogen, disrupted H3K9me2 domains, resulting in the spreading of H3K9me2 into active regions, which was associated with gene silencing. We found weak CCCTC-binding factor (CTCF)-binding sites and reduced CTCF binding at the Ni-disrupted H3K9me2 domain boundaries, suggesting a loss of CTCF-mediated insulation function as a potential reason for domain disruption and spreading. We furthermore show that euchromatin islands, local regions of active chromatin within large H3K9me2 domains, can protect genes from H3K9me2-spreadingM-bM-^@M-^Sassociated gene silencing. These results have major implications in understanding H3K9me2 dynamics and the consequences of chromatin domain disruption during pathogenesis.
2014-09-24 | E-GEOD-56053 | biostudies-arrayexpress
Project description:Alterations in chromatin modifications, including DNA methylation and histone modification patterns, have been characterized under exposure of several environmental pollutants, including nickel. As with other carcinogenic metals, the mutagenic potential of nickel compounds is low and is not well correlated with its carcinogenic effects. Nickel exposure, however, is associated with alterations in chromatin modifications and related transcriptional programs, suggesting an alternative pathway whereby nickel exposure can lead to disease. To investigate the extent to which nickel exposure disrupts chromatin patterns, we profiled several histone modifications, including H3K4me3, H3K9ac, H3K27me3 and H3K9me2 as well as the insulator binding protein CTCF and the transcriptomes of control BEAS-2B cells and cells treated with nickel for 72 hours. Our results show significant alterations of the repressive histone modification H3K9me2 in nickel-exposed cells with spreading of H3K9me2 into new domains associated with gene silencing. We furthermore show that local regions of active chromatin can protect genes from nickel-induced H3K9me2 spreading. Interestingly, we show that nickel exposure selectively disrupts weaker CTCF sites, leading to spreading of H3K9me2 at these regions. These results have major implications in the understanding of how environmental carcinogens can affect chromatin dynamics and the consequences of chromatin domain disruption in disease progression. Treat BEAS-2B cells with NiCl2 for 72 hours and compare histone modification, CTCF binding to control BEAS-2B cells to see how they regulated gene expression by RNA-seq
2014-09-26 | E-GEOD-56052 | biostudies-arrayexpress
Project description:Alterations in chromatin modifications, including DNA methylation and histone modification patterns, have been characterized under exposure of several environmental pollutants, including nickel. As with other carcinogenic metals, the mutagenic potential of nickel compounds is low and is not well correlated with its carcinogenic effects. Nickel exposure, however, is associated with alterations in chromatin modifications and related transcriptional programs, suggesting an alternative pathway whereby nickel exposure can lead to disease. To investigate the extent to which nickel exposure disrupts chromatin patterns, we profiled several histone modifications, including H3K4me3, H3K9ac, H3K27me3 and H3K9me2 as well as the insulator binding protein CTCF and the transcriptomes of control BEAS-2B cells and cells treated with nickel for 72 hours. Our results show significant alterations of the repressive histone modification H3K9me2 in nickel-exposed cells with spreading of H3K9me2 into new domains associated with gene silencing. We furthermore show that local regions of active chromatin can protect genes from nickel-induced H3K9me2 spreading. Interestingly, we show that nickel exposure selectively disrupts weaker CTCF sites, leading to spreading of H3K9me2 at these regions. These results have major implications in the understanding of how environmental carcinogens can affect chromatin dynamics and the consequences of chromatin domain disruption in disease progression. Treat BEAS-2B cells with NiCl2 for 72 hours and compare histone modification, CTCF binding to control BEAS-2B cells to see how they regulated gene expression by RNA-seq
2014-09-26 | E-GEOD-56051 | biostudies-arrayexpress
Project description:Human bronchial lung cells (BEAS-2B) were treated for 6 weeks with low doses (0.5 µg/mL) of Ni and NiO nanoparticles and NiCl2. At the end of the exposure control and treated samples were submitted for RNA-Seq analysis (Hiseq2500). The overall goal of this experiment was to gain an in-depth understanding of the transcriptomic changes induced by low-dose, long-term exposure of human lung cells to Ni and NiO nanoparticles as well as to NiCl2 and to generate hypotheses related to their mechanisms of toxicity.
2020-04-19 | E-MTAB-8903 | biostudies-arrayexpress
Project description:We have discovered that neutrophils that infiltrate the spinal cord of mice with EAE, a model of multiple sclerosis, but not intravascular neutrophils that crawl on the luminal endothelial surface, bear on their surface the adhesion molecule Icam1. The goal of this experiment was to use Icam1 to isolate these two neutrophil subpopulations in order to compare their transcriptomes and gain insights into their properties. To this end, EAE was induced in C57BL/6J mice by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (a.a. 35-55) and adjuvants (i.e. complete Freund’s adjuvant and pertussis toxin). On day 15 post-immunization, intravascular neutrophils (CD45hiCD11b+CD11c−Ly6g+Icam1−) and extravasated neutrophils (CD45hiCD11b+CD11c−Ly6g+Icam1+) were isolated from spinal cords by FACS. For comparison, we simultaneously isolated two other populations of myeloid cells: macrophages (CD45hiCD11b+CD11c−Ly6g−) and dendritic cells (CD45hiCD11b+CD11c+Ly6g−). RNA was analyzed in biological duplicate using Affymetrix GeneChip Mouse Gene 2.0 ST arrays.
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Project description:PCR array analysis was performed to investigate the expression of genes in the ear tissues of Ni allergy-induced miceand control mice.
2013-11-19 | GSE52466 | GEO
Project description:C56BL/6 mice (10 to 12-week-old) were immunized subcutaneously at the base of the tail with 100 μg of MOG (35–55) emulsified in complete Freund's adjuvant containing 500 μg of Mycobacterium tuberculosis. Pertussis toxin (200 ng; List Biological Laboratories) was injected intravenously at days 0 and 2 post-immunization. At day 17 post immunization, central nervous system CD45-positive immune cells were isolated and loaded onto a single channel of a 10x Chromium chip for each sample.
2022-06-06 | E-MTAB-11294 | biostudies-arrayexpress
Project description:C57BL/6 mice were immunized by subcutaneous injection of MOG35-55 peptide.DIM post-treatment was given at DAY 10 of the disease progression. CD4 T cells were isolated from the brain of the mice on day 15 of the MOG35-55 peptide immunization. Total RNA was extracted and subjected to microRNA high-throughput array with Affymetrix platform.
2013-11-01 | E-MTAB-2026 | biostudies-arrayexpress
Project description:To provide insights into the mode of action for Ni3S2 lung carcinogenicity by examining gene expression changes in target cells after inhalation exposure. Gene expression changes were determined in micro-dissected lung broncho-alveolar cells from Fischer F344 rats following inhalation of Ni3S2 at 0.0, 0.04, 0.08, 0.15, and 0.60 mg/m3 (0.03, 0.06, 0.11, and 0.44 mg Ni/m3) for one and four weeks (6 hours per day, 5 days per week). Results: Broncho-alveolar lavage fluid evaluation and lung histopathology provided evidence of inflammation only at the two highest concentrations, which were similar to those tested in the 2-year bioassay. The number of statistically significant up- and down-regulated genes decreased markedly from one to four weeks of exposure, suggesting adaptation. Cell signal pathway enrichment at both time-points primarily reflected responses to toxicity, including inflammatory and proliferative signaling. While proliferative signaling was up-regulated at both time points, some inflammatory signaling reversed from down-regulation at 1 week to up-regulation at 4 weeks. Conclusions: These results support a mode of action for Ni3S2 carcinogenicity driven by chronic toxicity, inflammation and proliferation, leading to mis-replication, rather than by direct genotoxicity. Benchmark dose (BMD) analysis identified the lowest pathway transcriptional BMD exposure concentration as 0.026 mg Ni/m3, for apoptosis/survival signaling. When conducted on the basis of lung Ni concentration the lowest pathway BMD was 0.64 M-BM-5g Ni/g lung, for immune/inflammatory signaling. Implications: These highly conservative BMDs could be used to derive a point of departure in a nonlinear risk assessment for Ni3S2 toxicity and carcinogenicity. Gene expression changes were determined in micro-dissected lung broncho-alveolar cells from Fischer F344 rats following inhalation of Ni3S2 at 0.0, 0.04, 0.08, 0.15, and 0.60 mg/m3 (0.03, 0.06, 0.11, and 0.44 mg Ni/m3) for one and four weeks (6 hours per day, 5 days per week).
2014-07-19 | E-GEOD-59593 | biostudies-arrayexpress
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