The methylome of Biomphalaria glabrata and other mollusks: enduring modification of epigenetic landscape and phenotypic traits by a new DNA methylation inhibitor

• Published in: Epigenetics & Chromatin
• Main Authors: Luviano, Nelia, Lopez, Marie, Gawehns, Fleur, Chaparro, Cristian, Arimondo, Paola B, Ivanovic, Slavica, David, Patrice, Verhoeven, Koen, Cosseau, Céline, Grunau, Christoph
• Other Authors: Interactions Hôtes-Pathogènes-Environnements (IHPE), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Perpignan Via Domitia (UPVD), Institut des Biomolécules Max Mousseron Pôle Chimie Balard (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE, Netherlands Institute of Ecology (NIOO-KNAW), Chimie biologique épigénétique - Epigenetic Chemical Biology (EpiCBio), Institut Pasteur Paris -Centre National de la Recherche Scientifique (CNRS), Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Université Paul-Valéry - Montpellier 3 (UPVM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD France-Sud )-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by Wellcome Trust strategic award 107475/Z/15/Z and by a PhD grant to NL from the Region Occitanie (EPIPARA project) and the University of Perpignan Via Domitia graduate school ED305. With the support of LabEx CeMEB, an ANR “Investissements d’avenir” program (ANR-10-LABX-04-01) through the Environmental Epigenomics Platform and the “projets de recherche exploratoires du CeMEB 2018” project “Epigenetics of inbreeding depression (EPID)”. This study is set within the framework of the “Laboratoires d'Excellences (LABEX)” TULIP (ANR‐10‐LABX‐41)., ANR-10-LABX-0004,CeMEB,Mediterranean Center for Environment and Biodiversity(2010), ANR-10-LABX-0041,TULIP,Towards a Unified theory of biotic Interactions: the roLe of environmental(2010)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2021
• Subjects: Invertebrates; Mollusks; Epimutation; Epigenetic inheritance; DNMT inhibitors; 5-Methylcytosine; [CHIM.THER]Chemical Sciences/Medicinal Chemistry; [SDV.BBM]Life Sciences [q-bio]/Biochemistry; Molecular Biology; [SDV]Life Sciences [q-bio]; [SDV.BDD]Life Sciences [q-bio]/Development Biology; Crassostrea gigas
• Online Access: https://hal-pasteur.archives-ouvertes.fr/pasteur-03427775; https://hal-pasteur.archives-ouvertes.fr/pasteur-03427775v2/document; https://hal-pasteur.archives-ouvertes.fr/pasteur-03427775v2/file/s13072-021-00422-7.pdf; https://doi.org/10.1186/s13072-021-00422-7

International audience Background 5-Methylcytosine (5mC) is an important epigenetic mark in eukaryotes. Little information about its role exists for invertebrates. To investigate the contribution of 5mC to phenotypic variation in invertebrates, alteration of methylation patterns needs to be produced. Here, we apply new non-nucleoside DNA methyltransferase inhibitors (DNMTi) to introduce aleatory changes into the methylome of mollusk species.Results Flavanone inhibitor Flv1 was efficient in reducing 5mC in the freshwater snails Biomphalaria glabrata and Physa acuta, and to a lesser degree, probably due to lower stability in sea water, in the oyster Crassostrea gigas . Flv1 has no toxic effects and significantly decreased the 5mC level in the treated B. glabrata and in its offspring. Drug treatment triggers significant variation in the shell height in both generations. A reduced representation bisulfite-sequencing method called epiGBS corroborates hypomethylation effect of Flv1 in both B. glabrata generations and identifies seven Differential Methylated Regions (DMR) out of 32 found both in Flv1-exposed snails and its progeny, from which 5 were hypomethylated, demonstrating a multigenerational effect. By targeted bisulfite sequencing, we confirmed hypomethylation in a locus and show that it is associated with reduced gene expression.Conclusions Flv1 is a new and efficient DNMTi that can be used to induce transient and heritable modifications of the epigenetic landscape and phenotypic traits in mollusks, a phylum of the invertebrates in which epigenetics is understudied.