Chemically Controlled Epigenome Editing through an Inducible dCas9 System

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 recruitmen...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2017-08, Vol.139 (33), p.11337-11340
Main Authors: Chen, Tingjun, Gao, Dan, Zhang, Roushu, Zeng, Guihua, Yan, Hao, Lim, Eunju, Liang, Fu-Sen
Format: Article
Language:English
Subjects:
Acetylation - drug effects
CRISPR-Cas Systems
E1A-Associated p300 Protein - genetics
Gene Editing - methods
Gene Targeting
Genetic Loci - drug effects
HEK293 Cells
Histone Code - drug effects
Histones - genetics
Humans
Small Molecule Libraries - pharmacology
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Summary: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.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.7b06555