Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Exposure to hycanthone alters chromatin structure around specific gene functions and specific repeats in Schistosoma mansoni.

Abstract : Schistosoma mansoni is a parasitic plathyhelminth responsible for intestinal schistosomiasis (or bilharzia), a disease affecting 67 million people worldwide and causing an important economic burden. The schistosomicides hycanthone, and its later proxy oxamniquine, were widely used for treatments in endemic areas during the twentieth century. Recently, the mechanism of action, as well as the genetic origin of a stably and Mendelian inherited resistance for both drugs was elucidated in two strains. However, several observations suggested early on that alternative mechanisms might exist, by which resistance could be induced for these two drugs in sensitive lines of schistosomes. This induced resistance appeared rapidly, within the first generation, but was metastable (not stably inherited). Epigenetic inheritance could explain such a phenomenon and we therefore re-analyzed the historical data with our current knowledge of epigenetics. In addition, we performed new experiments such as ChIP-seq on hycanthone treated worms. We found distinct chromatin structure changes between sensitive worms and induced resistant worms from the same strain. No specific pathway was discovered, but genes in which chromatin structure modifications were observed are mostly associated with transport and catabolism, which makes sense in the context of the elimination of the drug. Specific differences were observed in the repetitive compartment of the genome. We finally describe what types of experiments are needed to understand the complexity of heritability that can be based on genetic and/or epigenetic mechanisms for drug resistance in schistosomes
Liste complète des métadonnées

Littérature citée [64 références]  Voir  Masquer  Télécharger

https://hal-sde.archives-ouvertes.fr/hal-01112701
Contributeur : Anne Modat Connectez-vous pour contacter le contributeur
Soumis le : mercredi 7 août 2019 - 15:11:57
Dernière modification le : vendredi 17 décembre 2021 - 11:52:14
Archivage à long terme le : : jeudi 9 janvier 2020 - 09:00:56

Fichier

Roquis-2014-FrontiersGenet-Exp...
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Citation

David Roquis, Julie M. J. Lepesant, Emanuel Villafan, Jérôme Boissier, Cristina Vieira, et al.. Exposure to hycanthone alters chromatin structure around specific gene functions and specific repeats in Schistosoma mansoni.. Frontiers in Genetics, Frontiers, 2014, 5, pp.207. ⟨10.3389/fgene.2014.00207⟩. ⟨hal-01112701⟩

Partager

Métriques

Les métriques sont temporairement indisponibles