Department of Biomedical Engineering and Center for Genomic and Computational Biology, Duke University, Durham, North Carolina 27708, USA; email:
Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Annu Rev Genomics Hum Genet. 2018 Aug 31;19:43-71. doi: 10.1146/annurev-genom-083117-021632. Epub 2018 May 31.
The eukaryotic epigenome has an instrumental role in determining and maintaining cell identity and function. Epigenetic components such as DNA methylation, histone tail modifications, chromatin accessibility, and DNA architecture are tightly correlated with central cellular processes, while their dysregulation manifests in aberrant gene expression and disease. The ability to specifically edit the epigenome holds the promise of enhancing understanding of how epigenetic modifications function and enabling manipulation of cell phenotype for research or therapeutic purposes. Genome engineering technologies use highly specific DNA-targeting tools to precisely deposit epigenetic changes in a locus-specific manner, creating diverse epigenome editing platforms. This review summarizes these technologies and insights from recent studies, describes the complex relationship between epigenetic components and gene regulation, and highlights caveats and promises of the emerging field of epigenome editing, including applications for translational purposes, such as epigenetic therapy and regenerative medicine.
真核生物的表观基因组在决定和维持细胞特性和功能方面起着重要作用。表观遗传成分，如 DNA 甲基化、组蛋白尾部修饰、染色质可及性和 DNA 结构，与核心细胞过程密切相关，而其失调则表现为异常基因表达和疾病。特异性编辑表观基因组的能力有望增强我们对表观遗传修饰功能的理解，并能够操纵细胞表型，以用于研究或治疗目的。基因组编辑技术使用高度特异性的 DNA 靶向工具，以特定的方式在特定的基因座上精确地沉积表观遗传变化，从而创建多样化的表观基因组编辑平台。本综述总结了这些技术和最近研究的见解，描述了表观遗传成分与基因调控之间的复杂关系，并强调了新兴的表观基因组编辑领域的注意事项和前景，包括在转化应用方面的应用，如表观遗传学治疗和再生医学。
