Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNA-Seq of BEAS-2B cells treated with low doses of Ni and NiO nanoparticles as well as NiCl2 for 6 weeks

ABSTRACT: 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.

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Homo sapiens

SUBMITTER: Anda Gliga

PROVIDER: E-MTAB-8903 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transcriptome Profiling and Toxicity Following Long-Term, Low Dose Exposure of Human Lung Cells to Ni and NiO Nanoparticles-Comparison with NiCl<sub>2</sub>.

Gliga Anda R AR Di Bucchianico Sebastiano S Åkerlund Emma E Karlsson Hanna L HL

Nanomaterials (Basel, Switzerland) 20200331 4

Production of nickel (Ni) and nickel oxide (NiO) nanoparticles (NPs) leads to a risk of exposure and subsequent health effects. Understanding the toxicological effects and underlying mechanisms using relevant in vitro methods is, therefore, needed. The aim of this study is to explore changes in gene expression using RNA sequencing following long term (six weeks) low dose (0.5 µg Ni/mL) exposure of human lung cells (BEAS-2B) to Ni and NiO NPs as well as soluble NiCl<sub>2</sub>. Genotoxicity and ...[more]

PMID: 32244462

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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.

Dataset Information

RNA-Seq of BEAS-2B cells treated with low doses of Ni and NiO nanoparticles as well as NiCl2 for 6 weeks

Publications

Transcriptome Profiling and Toxicity Following Long-Term, Low Dose Exposure of Human Lung Cells to Ni and NiO Nanoparticles-Comparison with NiCl<sub>2</sub>.

Similar Datasets

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