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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)
1 Downloads (Pure)

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. Little is known about the mechanisms of inheritance of artificial environmental exposures. Camacho et al. describe the transgenerational reproductive dysfunctions caused by ancestral exposure to the model environmental compound Bisphenol A, and they provide a role for the regulation of repressive histone marks by histone demethylases in this process.

Original languageEnglish
Pages (from-to)2392-2404
Number of pages13
JournalCell Reports
Volume23
Issue number8
DOIs
Publication statusPublished - 22 May 2018
Externally publishedYes

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