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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Published inJournal of the American Chemical Society Vol. 139; no. 33; pp. 11337 - 11340
Main Authors Chen, Tingjun, Gao, Dan, Zhang, Roushu, Zeng, Guihua, Yan, Hao, Lim, Eunju, Liang, Fu-Sen
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 23.08.2017
Subjects
acetylation
Acetylation - drug effects
acetyltransferases
CRISPR-Cas Systems
E1A-Associated p300 Protein - genetics
gene activation
Gene Editing - methods
Gene Targeting
genes
Genetic Loci - drug effects
HEK293 Cells
Histone Code - drug effects
histones
Histones - genetics
Humans
loci
methodology
Small Molecule Libraries - pharmacology
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ISSN0002-7863
1520-5126
1520-5126
DOI10.1021/jacs.7b06555

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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.
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Tingjun Chen and Dan Gao contributed equally in this work.
ISSN:0002-7863
1520-5126
1520-5126
DOI:10.1021/jacs.7b06555