FN Archimer Export Format PT J TI The methylome of Biomphalaria glabrata and other mollusks: enduring modification of epigenetic landscape and phenotypic traits by a new DNA methylation inhibitor BT AF Luviano, Nelia Lopez, Marie Gawehns, Fleur Chaparro, Cristian Arimondo, Paola B. Ivanovic, Slavica David, Patrice Verhoeven, Koen Cosseau, Céline Grunau, Christoph AS 1:1;2:2,3;3:4;4:1;5:3,5;6:6;7:7;8:6;9:1;10:1; FF 1:;2:;3:;4:;5:;6:;7:;8:;9:;10:; C1 IHPE, Univ Perpignan Via Domitia, CNRC, Ifremer, Univ Montpellier, Perpignan, France Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Univ Montpellier, ENSCM, Montpellier, France Epigenetic Targeting of Cancer (ETaC), CNRS FRE3600, Centre de Recherche et Développement Pierre Fabre, Toulouse, France Bioinformatics Unit, Netherlands Institute of Ecology (NIOO-KNAW), Wageningen, The Netherlands Epigenetic Chemical Biology (EpiChBio), Department Structural Biology and Chemistry, UMR 3523, CNRS, Institute Pasteur, 75015, Paris, France Department of Terrestrial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), Wageningen, The Netherlands Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Univ. Montpellier, CNRS - Université Paul Valéry Montpellier - EPHE, 1919 Route de Mende, 34293, Montpellier Cedex 5, France C2 UNIV PERPIGNAN, FRANCE UNIV MONTPELLIER, FRANCE CNRS, FRANCE NIOO-KNAW, NETHERLANDS CNRS, FRANCE NIOO-KNAW, NETHERLANDS UNIV MONTPELLIER, FRANCE UM IHPE IN WOS Cotutelle UMR DOAJ copubli-france copubli-europe copubli-univ-france IF 5.488 TC 7 UR https://archimer.ifremer.fr/doc/00732/84361/89368.pdf https://archimer.ifremer.fr/doc/00732/84361/89369.xlsx LA English DT Article DE ;DNMT inhibitors;5-Methylcytosine;Mollusks;Invertebrates;Epigenetic inheritance;Epimutation AB 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. PY 2021 PD OCT SO Epigenetics & Chromatin SN 1756-8935 PU Springer Science and Business Media LLC VL 14 IS 1 UT 000711429200001 DI 10.1186/s13072-021-00422-7 ID 84361 ER EF