Chemically Controlled Epigenome Editing through an Inducible dCas9 System

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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

Substances

  • Histones
  • Small Molecule Libraries
  • E1A-Associated p300 Protein
  • EP300 protein, human