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

Nelia Luviano, Marie Lopez, Fleur Gawehns, Cristian Chaparro, Paola B. Arimondo, Slavica Ivanovic, Patrice David, Koen Verhoeven, Céline Cosseau, Christoph Grunau* (Corresponding author)

*Corresponding author for this work

Research output: Contribution to journal/periodicalArticleScientificpeer-review

7 Citations (Scopus)
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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.

Original languageEnglish
Article number48
Pages (from-to)48
JournalEpigenetics and Chromatin
Volume14
Issue number1
DOIs
Publication statusPublished - Dec 2021

Keywords

  • 5-Methylcytosine
  • DNMT inhibitors
  • Epigenetic inheritance
  • Epimutation
  • Invertebrates
  • Mollusks
  • international
  • Plan_S-Compliant-OA

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