Division of Chemical Biology and Medicinal Chemistry, Center for Integrative Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, Chapel Hill, NC 27514, USA.
Int J Mol Sci. 2020 Jan 31;21(3):943. doi: 10.3390/ijms21030943.
Proper regulation of the chromatin landscape is essential for maintaining eukaryotic cell identity and diverse cellular processes. The importance of the epigenome comes, in part, from the ability to influence gene expression through patterns in DNA methylation, histone tail modification, and chromatin architecture. Decades of research have associated this process of chromatin regulation and gene expression with human diseased states. With the goal of understanding how chromatin dysregulation contributes to disease, as well as preventing or reversing this type of dysregulation, a multidisciplinary effort has been launched to control the epigenome. Chemicals that alter the epigenome have been used in labs and in clinics since the 1970s, but more recently there has been a shift in this effort towards manipulating the chromatin landscape in a locus-specific manner. This review will provide an overview of chromatin biology to set the stage for the type of control being discussed, evaluate the recent technological advances made in controlling specific regions of chromatin, and consider the translational applications of these works.
正确调控染色质结构对于维持真核细胞的特性和多样化的细胞进程至关重要。表观基因组的重要性部分源于其通过 DNA 甲基化、组蛋白尾部修饰和染色质结构等模式来影响基因表达的能力。几十年来的研究已经将这种染色质调控和基因表达过程与人类疾病状态联系起来。为了了解染色质失调如何导致疾病，以及预防或逆转这种类型的失调，人们发起了一项多学科的努力来控制表观基因组。自 20 世纪 70 年代以来，改变表观基因组的化学物质一直在实验室和临床中使用，但最近，人们的努力方向发生了转变，开始以特定于基因座的方式来操纵染色质结构。本综述将提供染色质生物学的概述，为正在讨论的调控类型奠定基础，评估在控制特定染色质区域方面取得的最新技术进展，并考虑这些工作的转化应用。
