Cortés-Mancera Fabian M, Sarno Federica, Goubert Désirée, Rots Marianne G
Epigenetic Editing, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Grupo de Investigación e Innovación Biomédica, Departamento de Ciencias Aplicadas, Instituto Tecnológico Metropolitano, Medellín, Colombia.
Adv Exp Med Biol. 2022;1389:515-533. doi: 10.1007/978-3-031-11454-0_18.
DNA methylation is an essential epigenetic mark, strongly associated with gene expression regulation. Aberrant DNA methylation patterns underlie various diseases and efforts to intervene with DNA methylation signatures are of great clinical interest. Technological developments to target writers or erasers of DNA methylation to specific genomic loci by epigenetic editing resulted in successful gene expression modulation, also in in vivo models. Application of epigenetic editing in human health could have a huge impact, but clinical translation is still challenging. Despite successes for a wide variety of genes, not all genes mitotically maintain their (de)methylation signatures after editing, and reprogramming requires further understanding of chromatin context-dependency. In addition, difficulties of current delivery systems and off-target effects are hurdles to be tackled. The present review describes findings towards effective and sustained DNA (de)methylation by epigenetic editing and discusses the need for multi-effector approaches to achieve highly efficient long-lasting reprogramming.
DNA甲基化是一种重要的表观遗传标记，与基因表达调控密切相关。异常的DNA甲基化模式是多种疾病的基础，干预DNA甲基化特征的研究具有重要的临床意义。通过表观遗传编辑将DNA甲基化的写入者或擦除者靶向特定基因组位点的技术发展，已成功实现基因表达调控，在体内模型中也是如此。表观遗传编辑在人类健康领域的应用可能会产生巨大影响，但临床转化仍具有挑战性。尽管对多种基因取得了成功，但并非所有基因在编辑后都能有丝分裂地维持其（去）甲基化特征，重编程需要进一步了解染色质背景依赖性。此外，当前递送系统的困难和脱靶效应是有待解决的障碍。本综述描述了通过表观遗传编辑实现有效和持续DNA（去）甲基化的研究结果，并讨论了采用多效应器方法实现高效持久重编程的必要性。
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