DNA methylation and histone modifications are vital in maintaining genomic stability and modulating cellular functions in mammalian cells. These two epigenetic modifications are the most common gene regulatory systems known to spatially control gene expression. Transgene silencing by these two mechanisms is a major challenge to achieving effective gene therapy for many genetic conditions. The implications of transgene silencing caused by epigenetic modifications have been extensively studied and reported in numerous gene delivery studies. This review highlights instances of transgene silencing by DNA methylation and histone modification with specific focus on the role of these two epigenetic effects on the repression of transgene expression in mammalian cells from integrative and non-integrative based gene delivery systems in the context of gene therapy. It also discusses the prospects of achieving an effective and sustained transgene expression for future gene therapy applications.

中文翻译：

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基因治疗方面通过DNA甲基化和组蛋白修饰沉默哺乳动物细胞中的转基因表达。

DNA甲基化和组蛋白修饰对于维持基因组稳定性和调节哺乳动物细胞的细胞功能至关重要。这两个表观遗传修饰是已知的空间控制基因表达的最常见的基因调节系统。通过这两种机制进行的转基因沉默是在许多遗传条件下实现有效基因治疗的主要挑战。由表观遗传修饰引起的转基因沉默的含义已被广泛研究，并在众多基因递送研究中得到报道。这篇综述着重介绍了通过DNA甲基化和组蛋白修饰使转基因沉默的实例，特别着重于这两种表观遗传效应在基于基因治疗的整合和非整合基因递送系统中抑制哺乳动物细胞中转基因表达的作用。它还讨论了为将来的基因治疗应用实现有效和持续的转基因表达的前景。