Putative SET-domain methyltransferases in Cryptosporidium parvum and histone methylation during infection
Manasi Sawant,
Sadia Benamrouz-Vanneste,
Dionigia Meloni,
Nausicaa Gantois,
Gaël Even,
Karine Guyot,
Colette Creusy,
Erika Duval,
René Wintjens,
Jonathan B. Weitzman,
Magali Chabe,
Eric Viscogliosi,
Gabriela Certad
Affiliations
Manasi Sawant
Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 – CIIL – Centre d’Infection et d’Immunité de Lille, Lille, France
Sadia Benamrouz-Vanneste
Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 – CIIL – Centre d’Infection et d’Immunité de Lille, Lille, France
Dionigia Meloni
Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 – CIIL – Centre d’Infection et d’Immunité de Lille, Lille, France
Nausicaa Gantois
Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 – CIIL – Centre d’Infection et d’Immunité de Lille, Lille, France
Gaël Even
Gènes Diffusion, Douai, France
Karine Guyot
Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 – CIIL – Centre d’Infection et d’Immunité de Lille, Lille, France
Colette Creusy
Service d’Anatomie et de Cytologie Pathologiques, Groupement des Hôpitaux de l’Institut Catholique de Lille (GHICL), Lille, France
Erika Duval
Service d’Anatomie et de Cytologie Pathologiques, Groupement des Hôpitaux de l’Institut Catholique de Lille (GHICL), Lille, France
René Wintjens
Unit of Microbiology, Bioorganic and Macromolecular Chemistry, Department of Research in Drug Development (RD3), Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium
Jonathan B. Weitzman
UMR7216 Epigenetics and Cell, Université Paris Cité, Fate, CNRS, Paris, France
Magali Chabe
Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 – CIIL – Centre d’Infection et d’Immunité de Lille, Lille, France
Eric Viscogliosi
Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 – CIIL – Centre d’Infection et d’Immunité de Lille, Lille, France
Gabriela Certad
Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 – CIIL – Centre d’Infection et d’Immunité de Lille, Lille, France
Cryptosporidium parvum is a leading cause of diarrhoeal illness worldwide being a significant threat to young children and immunocompromised patients, but the pathogenesis caused by this parasite remains poorly understood. C. parvum was recently linked with oncogenesis. Notably, the mechanisms of gene expression regulation are unexplored in Cryptosporidium and little is known about how the parasite impact host genome regulation. Here, we investigated potential histone lysine methylation, a dynamic epigenetic modification, during the life cycle of the parasite. We identified SET-domain containing proteins, putative lysine methyltransferases (KMTs), in the C. parvum genome and classified them phylogenetically into distinct subfamilies (namely CpSET1, CpSET2, CpSET8, CpKMTox and CpAKMT). Our structural analysis further characterized CpSET1, CpSET2 and CpSET8 as histone lysine methyltransferases (HKMTs). The expression of the CpSET genes varies considerably during the parasite life cycle and specific methyl-lysine antibodies showed dynamic changes in parasite histone methylation during development (CpSET1:H3K4; CpSET2:H3K36; CpSET8:H4K20). We investigated the impact of C. parvum infection on the host histone lysine methylation. Remarkably, parasite infection led to a considerable decrease in host H3K36me3 and H3K27me3 levels, highlighting the potential of the parasite to exploit the host epigenetic regulation to its advantage. This is the first study to describe epigenetic mechanisms occurring throughout the parasite life cycle and during the host–parasite interaction. A better understanding of histone methylation in both parasite and host genomes may highlight novel infection control strategies.
