Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1269122 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transgenerational epigenetic inheritance and resetting of an environmentally-triggered change in gene expression in C. elegans
2024-09-28 | GSE74496 | GEO
Project description:How artificial environmental cues are biologically integrated and transgenerationally inherited is still poorly understood. Here, we investigate the mechanisms of inheritance of reproductive outcomes elicited by the model environmental chemical Bisphenol A (BPA) in C. elegans. We show that BPA exposure causes the derepression of an epigenetically silenced transgene in the germline for 5 generations, regardless of ancestral response. ChIP-seq, histone modifications quantitation, and immunofluorescence assays revealed that this effect is associated with a reduction of the repressive marks H3K9me3 and H3K27me3 in whole worms and in germline nuclei in the F3 as well as with reproductive dysfunctions including germline apoptosis and embryonic lethality. Furthermore, targeting of the Jumonji demethylases JMJD-2 and JMJD-3/UTX-1 restores H3K9me3 and H3K27me3 levels, respectively, and fully alleviates the BPA-induced transgenerational effects. Together, our results demonstrate the central role of repressive histone modifications in the inheritance of reproductive defects elicited by a common environmental chemical exposure.
2018-04-16 | GSE113187 | GEO
Project description:Adaptation to environmental stresses is crucial for survival. Transgenerational epigenetic inheritance allows organisms to respond to irregular conditions, alert their naïve descendants that stresses could still be present, and for distant descendants to eventually return to a basal state after several generations without the stress. However, it is still unclear whether organisms adapt on a transgenerational scale after repeated generational exposures to the same environmental stress. We recently found that C. elegans exposed to hypoxia in the parental (P0) generation: increased longevity in the P0 generation, caused an intergenerational reduction in lipids, and elicited a transgenerational reduction in fertility (P0-F2) that was dependent on small RNAs that were transmitted from parents to their naïve children. Here, we find that exposure of subsequent generations of C. elegans to hypoxia caused a transgenerational adaptation such that C. elegans that had repeated generational exposure to hypoxia failed to display hypoxia induced phenotypes. We show that upon two repeated generational exposures to hypoxia, C. elegans no longer display an increase in lifespan, and after four repeated generational exposures to hypoxia, C. elegans no longer display a decrease in reproduction. Transgenerational adaptation of the reproduction phenotype is dependent on the putative H3K27 trimethytransferase PRC2 complex and we identified critical genes that adapted on a transgenerational timeframe to repeated hypoxia exposure. Our findings reveal that transgenerational adaptation occurs and suggest that H3K27me3 is a critical modification for adapting to repeated generational stresses.
2025-09-19 | GSE255871 | GEO
Project description:How artificial environmental cues are biologically integrated and transgenerationally inherited is still poorly understood. Here, we investigate the mechanisms of inheritance of reproductive outcomes elicited by the model environmental chemical Bisphenol A (BPA) in C. elegans. We show that BPA exposure causes the derepression of an epigenetically silenced transgene in the germline for 5 generations, regardless of ancestral response. ChIP-seq, histone modifications quantitation, and immunofluorescence assays revealed that this effect is associated with a reduction of the repressive marks H3K9me3 and H3K27me3 in whole worms and in germline nuclei in the F3 as well as with reproductive dysfunctions including germline apoptosis and embryonic lethality. Furthermore, targeting of the Jumonji demethylases JMJD-2 and JMJD-3/UTX-1 restores H3K9me3 and H3K27me3 levels, respectively, and fully alleviates the BPA-induced transgenerational effects. Together, our results demonstrate the central role of repressive histone modifications in the inheritance of reproductive defects elicited by a common environmental chemical exposure.
2018-04-17 | GSE113266 | GEO
Project description:Exposure to TCDD early in development produces reproductive abnormalities and decreased reproductive capacity in males in subsequent generations. We used WGBS to investigate differential methylation in testicular tissue and identified distinct multigenerational and transgenerational methylation changes due to legacy TCDD exposure in males.
2022-04-20 | GSE149919 | GEO
Project description:Di(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer and known endocrine disrupting chemical, which causes transgenerational reproductive toxicity in female rodents. However, the mechanisms of action underlying the transgenerational toxicity of DEHP are not understood. Therefore, this study determined the effects of prenatal and ancestral DEHP exposure on various ovarian pathways in the F1, F2, and F3 generations of mice. Pregnant CD-1 dams were orally exposed to corn oil (vehicle control) or DEHP (20 μg/kg/day-750 mg/kg/day) from gestation day 10.5 until birth. At postnatal day 21 for all generations, ovaries were removed for gene expression analysis of various ovarian pathways and for 5-methyl cytosine (5-mC) quantification. In the F1 generation, prenatal DEHP exposure disrupted the expression of cell cycle regulators, the expression of peroxisome-proliferator activating receptors, and the percentage of 5-mC compared to control. In the F2 generation, exposure to DEHP decreased the expression of steroidogenic enzymes, apoptosis factors, and ten-eleven translocation compared to controls. It also dysregulated the expression of phosphoinositide 3-kinase (PI3K) factors. In the F3 generation, ancestral DEHP exposure decreased the expression of steroidogenic enzymes, PI3K factors, cell cycle regulators, apoptosis factors, Esr2, DNA methylation mediators, and the percentage of 5-mC compared to controls. Overall, the data show that prenatal and ancestral DEHP exposure greatly suppress gene expression of pathways required for folliculogenesis and steroidogenesis in the ovary in a transgenerational manner and that gene expression may be influenced by DNA methylation. These results provide insight into some of the mechanisms of DEHP-mediated toxicity in the ovary across generations.
2020-09-22 | GSE158266 | GEO
Project description:Organisms can develop adaptive sequence-specific immunity by reexpressing pathogen-specific small RNAs that guide gene silencing. For example, the C. elegans PIWI-Argonaute/piwi-interacting RNA (piRNA) pathway recruits RNA-dependent RNA polymerase (RdRP) to foreign sequences to amplify a transgenerational small-RNA-induced epigenetic silencing signal (termed RNAe). Here, we provide evidence that, in addition to an adaptive memory of silenced sequences, C. elegans can also develop an opposing adaptive memory of expressed/self-mRNAs. We refer to this mechanism, which can prevent or reverse RNAe, as RNA-induced epigenetic gene activation (RNAa). We show that CSR-1, which engages RdRP-amplified small RNAs complementary to germline-expressed mRNAs, is required for RNAa. We show that a transgene with RNAa activity also exhibits accumulation of cognate CSR-1 small RNAs. Our findings suggest that C. elegans adaptively acquires and maintains a transgenerational CSR-1 memory that recognizes and protects self-mRNAs, allowing piRNAs to recognize foreign sequences innately, without the need for prior exposure.
2013-12-23 | GSE49532 | GEO