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EPIGENETIC CONTROL OF GENE FUNCTION IN SCHISTOSOMES: A SOURCE OF THERAPEUTIC TARGETS?
schistosome
drug discovery
histone modifying enzymes
DNA methylation
microRNAs
Autor(es)
Afiliação
Université de Lille. Institut National de la Santé et de la Recherche Médicale. Centre National de la Recherche Scientifique. Institut Pasteur de Lille. Center for Infection and Immunity of Lille. Lille, France
Université de Lille. Institut National de la Santé et de la Recherche Médicale. Centre National de la Recherche Scientifique. Institut Pasteur de Lille. Center for Infection and Immunity of Lille. Lille, France
Université de Lille. Institut National de la Santé et de la Recherche Médicale. Centre National de la Recherche Scientifique. Institut Pasteur de Lille. Center for Infection and Immunity of Lille. Lille, France
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Centro de Excelencia em Bioinformatica. Grupo de Biologia e Genômica Computational. Instituto Nacional de Ciencia e Tecnologia em Doenças Tropicais. Belo Horizonte, MG, Brazil
Université de Lille. Institut National de la Santé et de la Recherche Médicale. Centre National de la Recherche Scientifique. Institut Pasteur de Lille. Center for Infection and Immunity of Lille. Lille, France
Université de Lille. Institut National de la Santé et de la Recherche Médicale. Centre National de la Recherche Scientifique. Institut Pasteur de Lille. Center for Infection and Immunity of Lille. Lille, France
Université de Lille. Institut National de la Santé et de la Recherche Médicale. Centre National de la Recherche Scientifique. Institut Pasteur de Lille. Center for Infection and Immunity of Lille. Lille, France
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Centro de Excelencia em Bioinformatica. Grupo de Biologia e Genômica Computational. Instituto Nacional de Ciencia e Tecnologia em Doenças Tropicais. Belo Horizonte, MG, Brazil
Université de Lille. Institut National de la Santé et de la Recherche Médicale. Centre National de la Recherche Scientifique. Institut Pasteur de Lille. Center for Infection and Immunity of Lille. Lille, France
Resumo em Inglês
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.
Palavras-chave em inglês
epigeneticsschistosome
drug discovery
histone modifying enzymes
DNA methylation
microRNAs
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