Luviano Nelia, Duval David, Ittiprasert Wannaporn, Allienne Jean-Francois, Tavernier Geneviève, Chaparro Cristian, Cosseau Celine, Grunau Christoph
IHPE, Univ Perpignan Via Domitia, CNRS, Ifremer, Univ Montpellier, Perpignan, France.
Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States.
Front Cell Dev Biol. 2022 Feb 28;10:794650. doi: 10.3389/fcell.2022.794650. eCollection 2022.
Snail-borne parasitic diseases represent an important challenge to human and animal health. Control strategies that target the intermediate snail host has proved very effective. Epigenetic mechanisms are involved in developmental processes and therefore play a fundamental role in developmental variation. DNA methylation is an important epigenetic information carrier in eukaryotes that plays a major role in the control of chromatin structure. Epigenome editing tools have been instrumental to demonstrate functional importance of this mark for gene expression in vertebrates. In invertebrates, such tools are missing, and the role of DNA methylation remains unknown. Here we demonstrate that methylome engineering can be used to modify the CpG methylation level of a target gene in the freshwater snail intermediate host of the human parasite . We used a dCas9-SunTag-DNMT3A complex and synthetic sgRNA to transfect embryos and observed an increase of CpG methylation at the target site in 50% of the hatching snails.
蜗牛传播的寄生虫病对人类和动物健康构成了重大挑战。事实证明,针对中间宿主蜗牛的控制策略非常有效。表观遗传机制参与发育过程,因此在发育变异中起着基础性作用。DNA甲基化是真核生物中一种重要的表观遗传信息载体,在染色质结构控制中起主要作用。表观基因组编辑工具有助于证明这种标记对脊椎动物基因表达的功能重要性。在无脊椎动物中,缺少此类工具,DNA甲基化的作用仍然未知。在这里,我们证明了甲基化组工程可用于改变人类寄生虫淡水蜗牛中间宿主中靶基因的CpG甲基化水平。我们使用dCas9-SunTag-DNMT3A复合物和合成sgRNA转染胚胎,并在50%的孵化蜗牛中观察到靶位点的CpG甲基化增加。