In complex multicellular systems, gene expression is regulated at multiple stages through interconnected complex molecular pathways and regulatory networks. Transcription is the first step in gene expression and is subject to multiple layers of regulation in which epigenetic mechanisms such as DNA methylation, histone tail modifications, and chromosomal conformation play an essential role. In recent years, CRISPR-Cas9 systems have been employed to unearth this complexity and provide new insights on the contribution of chromatin dysregulation in the development of genetic diseases, as well as new tools to prevent or reverse this dysregulation. In this review, we outline the recent development of a variety of CRISPR-based epigenetic editors for targeted DNA methylation/demethylation, histone modification, and three-dimensional DNA conformational change, highlighting their relative performance and impact on gene regulation. Finally, we provide insights on the future developments aimed to accelerate our understanding of the causal relationship between epigenetic marks, genome organization, and gene regulation.

中文翻译：

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基因表达的调控以及基于 CRISPR 的表观遗传修饰符和 CRISPR 诱导的染色体构象变化的阐明作用

在复杂的多细胞系统中，基因表达通过相互关联的复杂分子通路和调控网络在多个阶段受到调控。转录是基因表达的第一步，受多层调控，其中 DNA 甲基化、组蛋白尾部修饰和染色体构象等表观遗传机制起着至关重要的作用。近年来，CRISPR-Cas9 系统已被用于发掘这种复杂性，并提供关于染色质失调在遗传疾病发展中的贡献的新见解，以及预防或逆转这种失调的新工具。在这篇综述中，我们概述了各种基于 CRISPR 的表观遗传编辑器的最新发展，用于靶向 DNA 甲基化/去甲基化、组蛋白修饰、和三维 DNA 构象变化，突出了它们的相对性能和对基因调控的影响。最后，我们提供了对未来发展的见解，旨在加速我们对表观遗传标记、基因组组织和基因调控之间因果关系的理解。