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
Affiliations
Jessica Camacho
Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA
Lisa Truong
Human Genetics and Genomic Analysis Training Program, University of California, Los Angeles, Los Angeles, CA 90095, USA
Zeyneb Kurt
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA
Yen-Wei Chen
Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA
Marco Morselli
Molecular, Cell and Developmental Biology Department, University of California, Los Angeles, Los Angeles, CA 90095, USA
Gerardo Gutierrez
Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Environmental and Occupational Health, California State University, Northridge, CA 91330, USA
Matteo Pellegrini
Molecular, Cell and Developmental Biology Department, University of California, Los Angeles, Los Angeles, CA 90095, USA
Xia Yang
Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
Patrick Allard
Molecular Toxicology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Society and Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Corresponding author
Summary: 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. Keywords: C. elegans, transgenerational inheritance, reproductive function, Bisphenol A, histone demethylase, epigenetic
