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

TY - JOUR

T1 - The methylome of Biomphalaria glabrata and other mollusks

T2 - enduring modification of epigenetic landscape and phenotypic traits by a new DNA methylation inhibitor

AU - Luviano, Nelia

AU - Lopez, Marie

AU - Gawehns, Fleur

AU - Chaparro, Cristian

AU - Arimondo, Paola B.

AU - Ivanovic, Slavica

AU - David, Patrice

AU - Verhoeven, Koen

AU - Cosseau, Céline

AU - Grunau, Christoph

N1 - 7323, TE

PY - 2021/12

Y1 - 2021/12

N2 - 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.

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.

KW - 5-Methylcytosine

KW - DNMT inhibitors

KW - Epigenetic inheritance

KW - Epimutation

KW - Invertebrates

KW - Mollusks

KW - international

KW - Plan_S-Compliant-OA

U2 - 10.1186/s13072-021-00422-7

DO - 10.1186/s13072-021-00422-7

M3 - Article

C2 - 34702322

AN - SCOPUS:85118206230

SN - 1756-8935

VL - 14

SP - 48

JO - Epigenetics and Chromatin

JF - Epigenetics and Chromatin

IS - 1

M1 - 48

ER -