Getting a handle on chemical probes of chomatin readers.
Getting a handle on chemical probes of chomatin readers.
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DOI：
10.4155/fmc-2019-0274
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发表时间：
2020-01
影响因子：
4.2
通讯作者：
J. Waybright;L. James
中科院分区：
文献类型：
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作者：
J. Waybright;L. James
组蛋白翻译后修饰（如甲基化或乙酰化）的动态特性使得通过操纵相关表观遗传机制来改变疾病相关表观遗传状态成为可能。一种方法是通过小分子扰动。表观遗传解读域的化学探针在提高我们对调节其靶标的生物学后果的理解方面至关重要，同时也使新型探针试剂的开发成为可能。通过在阅读器结构域探针上附加一个功能手柄，可以创建一个化学试剂工具箱，以促进表观遗传复合物的化学沉淀，评估探针选择性，开发体外筛选试验，可视化细胞靶标定位，使靶标降解和以高度控制的方式将表观遗传机制招募到基因组内的一个位点。
The dynamic nature of histone post-translational modifications such as methylation or acetylation makes possible the alteration of disease associated epigenetic states through the manipulation of the associated epigenetic machinery. One approach is through small molecule perturbation. Chemical probes of epigenetic reader domains have been critical in improving our understanding of the biological consequences of modulating their targets, while also enabling the development of novel probe-based reagents. By appending a functional handle to a reader domain probe, a chemical toolbox of reagents can be created to facilitate chemiprecipitation of epigenetic complexes, evaluate probe selectivity, develop in vitro screening assays, visualize cellular target localization, enable target degradation and recruit epigenetic machinery to a site within the genome in a highly controlled fashion.