设计表观基因组编辑器：生化特异性和位点特异性的考量
Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.
作者信息
Sen Dilara, Keung Albert J
机构信息
Chemical and Biomolecular Engineering Department, North Carolina State University, Raleigh, NC, USA.
W. M. Keck Center for Behavioral Biology, Genetics Program, North Carolina State University, Raleigh, NC, USA.
出版信息
Methods Mol Biol. 2018;1767:65-87. doi: 10.1007/978-1-4939-7774-1_3.
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.
位点特异性蛋白质招募技术的出现开启了染色质生物学领域的一类新研究。表观基因组编辑器能够对几乎任何特定的内源性位点进行染色质的生化修饰。它们的位点特异性揭示了独特的信息，包括特定基因组位点上不同修饰的功能作用。鉴于对将这些工具用于生物学和转化研究的兴趣日益浓厚，根据科学问题或临床需求存在许多具体的设计考量。在此，我们提出并讨论关于表观基因组编辑器的生化和位点特异性的重要设计考量及挑战。这些包括如何考虑染色质复杂的生化多样性；控制表观基因组编辑器及其产生的修饰之间潜在的相互依赖性；避免隔离效应；量化表观基因组编辑器的位点特异性；以及通过考虑浓度、亲和力、亲合力和隔离效应来提高位点特异性。
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