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通过诱导型 dCas9 系统实现化学控制的表观基因组编辑。

Chemically Controlled Epigenome Editing through an Inducible dCas9 System.

机构信息

Department of Chemistry and Chemical Biology, University of New Mexico , 300 Terrace Street NE, Albuquerque, New Mexico 87131, United States.

出版信息

J Am Chem Soc. 2017 Aug 23;139(33):11337-11340. doi: 10.1021/jacs.7b06555. Epub 2017 Aug 10.

Abstract

Although histone modifications are associated with gene activities, studies of their causal relationships have been difficult. For this purpose, we developed an inducible system integrating dCas9-based targeting and chemically induced proximity technologies to allow small molecule induced recruitment of P300 acetyltransferase and the acetylation of H3K27 at precise gene loci in cells. Employing the new technique, we elucidated the temporal order of histone acetylation and gene activation, as well as the stability of the installed histone modification.

摘要

虽然组蛋白修饰与基因活性有关,但研究它们的因果关系一直很困难。为此,我们开发了一种诱导系统,整合了基于 dCas9 的靶向和化学诱导接近技术,以允许小分子诱导 P300 乙酰转移酶的募集,并在细胞中精确的基因位点乙酰化 H3K27。利用新技术,我们阐明了组蛋白乙酰化和基因激活的时间顺序,以及安装的组蛋白修饰的稳定性。

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