title: Chronic MeHg exposure modifies the histone H3K4me3 epigenetic landscape in Caenorhabditis elegans.
abstract: Methylmercury (MeHg) is a persistent environmental pollutant that occurs in the food chain, at occupational sites, and via medical procedures. Exposure in humans and animal models results in renal, neuro, and reproductive toxicities. In this study, we demonstrate that chronic exposure to MeHg (10μM) causes epigenetic landscape modifications of histone H3K4 trimethylation (H3K4me3) marks in Caenorhabditis elegans using chromatin immuno-precipitation sequencing (ChIP-seq). The modifications correspond to the locations of 1467 genes with enhanced and 508 genes with reduced signals. Among enhanced genes are those encoding glutathione-S-transferases, lipocalin-related protein and a cuticular collagen. ChIP-seq enhancement of these genes was confirmed with increased mRNA expression levels revealed by qRT-PCR. Furthermore, we observed enhancement of H3K4me3 marks in these genes in animals exposed to MeHg in utero and assayed at L4 stage. In utero exposure enhanced marks without alterations in mRNA expression except for the lpr-5 gene. Finally, knockdown of lipocalin-related protein gene lpr-5, which is involved in intercellular signaling, and cuticular collagen gene dpy-7, structural component of the cuticle, by RNA interference (RNAi) resulted in increased lethality of animals after MeHg exposure. Our results provide new data on the epigenetic landscape changes elicited by MeHg exposure, as well as describe a unique model for studying in utero effects of heavy metals. Together, these findings may help to understand the toxicological effects of MeHg at the molecular level.
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio, Finland; Faculty of Health Sciences, University of Macau, Macau, S.A.R., China.
authors.forename: Martina
authors.initials: M
authors.lastname: Rudgalvyte
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Juhani
authors.initials: J
authors.lastname: Peltonen
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Merja
authors.initials: M
authors.lastname: Lakso
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, S.A.R., China. Electronic address: Garry.Wong@uef.fi.
authors.forename: Garry
authors.initials: G
authors.lastname: Wong
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D008767:Methylmercury Compounds / Q000633:toxicity*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D029742:Caenorhabditis elegans Proteins; D004785:Environmental Pollutants; D006657:Histones; D008767:Methylmercury Compounds; D012333:RNA, Messenger
keywords: Chromatin immunoprecipitation sequencing (ChIP-seq); Epigenetics; Heavy metal; Mercury; RNA sequencing (RNA-seq)