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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: The Memory of Environmental Chemical Exposure in C. elegans Is Dependent on the Jumonji Demethylases jmjd-2 and jmjd-3/utx-1.

Authors: Camacho, Jessica; Truong, Lisa; Kurt, Zeyneb; Chen, Yen-Wei; Morselli, Marco; Gutierrez, Gerardo; Pellegrini, Matteo; Yang, Xia; Allard, Patrick

Published In Cell Rep, (2018 05 22)

Abstract: 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 in C. elegans. We show that Bisphenol A (BPA) exposure causes the derepression of an epigenomically silenced transgene in the germline for 5 generations, regardless of ancestral response. Chromatin immunoprecipitation sequencing (ChIP-seq), histone modification 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 it 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.

PubMed ID: 29791850 Exiting the NIEHS site

MeSH Terms: Animals; Benzhydryl Compounds/toxicity; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism*; Caenorhabditis elegans/drug effects; Caenorhabditis elegans/embryology; Caenorhabditis elegans/genetics; Caenorhabditis elegans/physiology*; Embryo, Nonmammalian/drug effects; Embryo, Nonmammalian/metabolism; Environment*; Fertility/drug effects; Germ Cells/metabolism; Histone Code; Histone Demethylases/genetics; Histone Demethylases/metabolism*; Histones/metabolism; Inheritance Patterns/genetics; Lysine/metabolism; Memory*; Methylation; Phenols/toxicity; Transcriptome/genetics; Transgenes; Up-Regulation/drug effects; Up-Regulation/genetics

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