Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.
Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.
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DOI：
10.1007/978-1-4939-7774-1_3
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Keung AJ
中科院分区：
文献类型：
--
作者：
Sen D;Keung AJ
基因座特异性蛋白质募集技术的出现使染色质生物学研究成为可能。表观基因组编辑器能够在几乎任何特定的内源基因座处对染色质进行生化修饰。它们的基因座特异性解锁了独特的信息，包括在特定基因组基因座的不同修饰的功能作用。鉴于人们对使用这些工具进行生物学和转化研究的兴趣越来越大，根据科学问题或临床需求，有许多具体的设计考虑。在这里，我们提出并讨论了重要的设计考虑和挑战的生化和基因座特异性的表观基因组编辑。其中包括如何：解释染色质的复杂生化多样性;控制表观基因组编辑及其所得修饰的潜在相互依赖性;避免隔离效应;量化表观基因组编辑的基因座特异性;以及通过考虑浓度、亲和力、亲合力和隔离效应来提高基因座特异性。
The advent of locus-specific protein recruitment technologies has enabled a new class of studies in chromatin biology. Epigenome editors enable biochemical modifications of chromatin at almost any specific endogenous locus. Their locus-specificity unlocks unique information including the functional roles of distinct modifications at specific genomic loci. Given the growing interest in using these tools for biological and translational studies, there are many specific design considerations depending on the scientific question or clinical need. Here we present and discuss important design considerations and challenges regarding the biochemical- and locus-specificities of epigenome editors. These include how to: account for the complex biochemical diversity of chromatin; control for potential interdependency of epigenome editors and their resultant modifications; avoid sequestration effects; quantify the locus specificity of epigenome editors; and improve locus-specificity by considering concentration, affinity, avidity, and sequestration effects.