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Bacterial diet and weak cadmium stress affect the age-specific survival rates of Caenorhabditis elegans and its resistance against severe stressors

ABSTRACT: Bacterial diet and weak cadmium stress affect the age-specific survival rates of Caenorhabditis elegans and its resistance against severe stressors

PROVIDER: PRJNA507775 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8268210.fastq.gz	Fastqsanger.gz
	SRR8268211.fastq.gz	Fastqsanger.gz
	SRR8268212.fastq.gz	Fastqsanger.gz
	SRR8268203.fastq.gz	Fastqsanger.gz
	SRR8268213.fastq.gz	Fastqsanger.gz

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Project description:Background: Imprinted genes are defined by their preferential expression from one of the two parental alleles. This unique mode of gene expression is dependent on allele-specific DNA methylation profiles established at regulatory sequences called imprinting control regions. These loci are frequently used as biosensors to study how environmental exposures affect methylation and transcription. However, a critical unanswered question is whether they are more, less or equally sensitive to environmental stressors as the rest of the genome. Objectives: Using cadmium exposure in humans as a model, we determined the relative sensitivity of imprinting control regions to perturbation of methylation compared to similar, non-imprinted loci in the genome. Methods: We assayed DNA methylation genome-wide using bisulfite sequencing of newborn cord blood and maternal blood samples selected on the basis of maternal blood cadmium levels. Differentially methylated regions associated with cadmium exposure were identified. Results: In newborn cord blood and maternal blood, 641 and 1945 cadmium-associated differentially methylated regions were identified, respectively. These were strongly enriched at maternally-methylated imprinting control regions when compared to similar loci in newborn cord blood (P = 5.64E-8) and maternal blood (P = 6.22E-14), suggesting an increased sensitivity for imprinting control regions to cadmium. Genome-wide, methylation changes were enriched in maternal blood at genes implicated in body mass index (P = 2.0E-5), blood pressure (P = 3.8E-5) and body weight (P = 1.4E-3), with similar trends for metabolic and cardiovascular functions in cord blood, suggesting that epigenetic changes may contribute to the etiology of cadmium-associated diseases. Conclusions: We present the first global nucleotide-resolution DNA methylation profile associated with cadmium exposure in humans. We identify imprinting control regions as hotspots for perturbation by cadmium, possibly due to their unique modes of regulation, motivating further study of these loci to provide insight into the mechanisms of cadmium action.

Project description:Our main objectives were: 1) to identify transcriptional signatures specific to the exposure to two metals: Ni and Cd; 2) to investigate the mechanisms of toxicity for these two metals; and 3) to develop a predictive tool to identify the sublethal effects of Ni and Cd contaminants in fish sampled from natural environments. The molecular mechanisms underlying nickel (Ni) and cadmium (Cd) toxicity and their specific effects on fish are poorly understood. Documenting gene transcription profiles offers a powerful approach towards identifying the molecular mechanisms affected by these metals and to discover biomarkers of their toxicity. However, confounding environmental factors can complicate the interpretation of the results and the detection of biomarkers for fish captured in their natural environment. In the present study, a 1000 candidate-gene microarray, developed from a previous RNA-seq study on a subset of individual fish from contrasting level of metal contamination, was used to investigate the transcriptional response to metal (Ni and Cd) and non metal (temperature, oxygen, and diet) stressors in yellow perch (Perca flavescens). Specifically, we aimed at 1) identifying transcriptional signatures specific to Ni and Cd exposure, 2) investigating the mechanisms of their toxicity, and 3) developing a predictive tool to identify the sublethal effects of Ni and Cd contaminants in fish sampled from natural environments. A total of 479 genes displayed significantly different transcription levels when temperature varied while 287 and 177 genes were differentially transcribed at different concentrations of Ni and Cd, respectively. These metals were found to mainly affect the transcription level of genes involved in iron metabolism, transcriptional and translational processes, vitamin metabolism, blood coagulation, and calcium transport. In addition, a linear discriminant analysis (LDA) made using gene transcription levels yielded 94% correctly reassigned samples regarding their level of metal contamination, which indicates the potential of the microarray to detect perch response to Cd or Ni effects. Comparison between fish exposed to three temperatures (11, 20, 28M-BM-0C) using a loop design, comparison between control fish and fich exposed to restrictive diet using a pairwise design, comparison between fish exposed to hypoxia and control fish, comparison between fish exposed to two concentrations of cadmium and control fish using a loop design, and comparison between fish exposed to two concentrations of nickel and control fish using a loop design.

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Bacterial diet and weak cadmium stress affect the age-specific survival rates of Caenorhabditis elegans and its resistance against severe stressors

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