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

Epigenetics & Chromatin

Fleur Gawehns¹  Patrice David²  Koen Verhoeven³  Slavica Ivanovic³  Paola B. Arimondo⁴  Christoph Grunau⁵  Nelia Luviano⁵  Céline Cosseau⁵  Cristian Chaparro⁵  Marie Lopez⁶ 

[1] Bioinformatics Unit, Netherlands Institute of Ecology (NIOO-KNAW);Centre d’Ecologie Fonctionnelle et Evolutive (CEFE), Univ. Montpellier, CNRS - Université Paul Valéry Montpellier - EPHE;Department of Terrestrial Ecology, Netherlands Institute of Ecology (NIOO-KNAW);Epigenetic Targeting of Cancer (ETaC), CNRS FRE3600, Centre de Recherche et Développement Pierre Fabre;IHPE, Univ Perpignan Via Domitia, CNRC, Ifremer, Univ Montpellier;Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Univ Montpellier, ENSCM;

关键词: DNMT inhibitors;    5-Methylcytosine;    Mollusks;    Invertebrates;    Epigenetic inheritance;    Epimutation;   

DOI  :  10.1186/s13072-021-00422-7

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown