title: Epigenetic control of gene function in schistosomes: a source of therapeutic targets?
abstract: The discovery of the epigenetic regulation of gene expression has revolutionized both our understanding of how genomes function and approaches to the therapy of numerous pathologies. Schistosomes are metazoan parasites and as such utilize most, if not all the epigenetic mechanisms in play in their vertebrate hosts: histone variants, histone tail modifications, non-coding RNA and, perhaps, DNA methylation. Moreover, we are acquiring an increasing understanding of the ways in which these mechanisms come into play during the complex schistosome developmental program. In turn, interest in the actors involved in epigenetic mechanisms, particularly the enzymes that carry out epigenetic modifications of histones or nucleic acid, as therapeutic targets has been stimulated by the finding that their inhibitors exert profound effects, not only on survival, but also on the reproductive function of Schistosoma mansoni. Here, we review our current knowledge, and what we can infer, about the role of epigenetic mechanisms in schistosome development, differentiation and survival. We will consider which epigenetic actors can be targeted for drug discovery and what strategies can be employed to develop potent, selective inhibitors as drugs to cure schistosomiasis.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1019 - Centre National de la Recherche Scientifique UMR 8204, Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Université de Lille Lille, France.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cabezas-Cruz
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1019 - Centre National de la Recherche Scientifique UMR 8204, Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Université de Lille Lille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Lancelot
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1019 - Centre National de la Recherche Scientifique UMR 8204, Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Université de Lille Lille, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Caby
authors.affiliation: Genomics and Computational Biology Group, Fundação Oswaldo Cruz, Center for Excellence in Bioinformatics, Centro de Pesquisas René Rachou, National Institute of Science and Technology in Tropical Diseases Belo Horizonte, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Oliveira
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1019 - Centre National de la Recherche Scientifique UMR 8204, Center for Infection and Immunity of Lille, Institut Pasteur de Lille, Université de Lille Lille, France.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Pierce
keywords: DNA methylation; drug discovery; epigenetics; histone modifying enzymes; microRNAs; schistosome