Chemical Inducible dCas9-Guided Editing of H3K27 Acetylation in Mammalian Cells.

Abstract

The ability to edit specific epigenetic modifications at defined gene loci is pivotal to understand the biological function of these epigenetic marks. Here we describe a new inducible method to integrate the dCas9-based genome targeting with abscisic acid (ABA)-based chemically induced proximity (CIP) technologies to modify histone tail modifications at specific genome loci in living cells. ABA leads to rapid hetero-dimerization of the PYL and ABI proteins, which can be individually fused to dCas9 and a histone-modifying enzyme core domain. In the presence of ABA and locus-specific sgRNAs, this histone-modifying activity can be recruited to a specific genome locus to achieve histone editing with perfect temporal control. Herein, we describe the use of this technique in HEK293T cells to control the recruitment of the p300 acetyltransferase core domain to the human IL1RN locus to ectopically increase the acetylation of H3K27 and induce the expression of IL1RN gene.