Temporal and spatial epigenome editing
allows precise gene regulation
ML-05.02.2-002
M. AdliI
IUniversity of Virginia, charlottesville, United States of America
Ability to precisely control the expression a gene in the human genome has great
implications for basic and clinical research. Here, we develop and utilize CRISPR
based epigenetic tools and alternative targeting approaches to control the temporal
duration as well as the intensity of gene expression through epigenome editing. To
control temporal gene expression and study the induced epigenetic memory, we
integrated locus specific epigenome editing tool with plant based auxin-induced
degradation (AID) system. To control the amplitude of gene expression from a
specifically targated endogenous locus, we used dCas9-P300 epigenetic editing tool to
reprogram non-regulatory distal genomic regions into enhancer-like elements. We show
that by controlling the target site distance to the promoter region, the gene
expression intensity can be precisely regulated through such “induced enhancer”
(IE) sites. These approaches allow novel insight into gene regulation from distal
regulatory sites and epigenetic memory induced by specific epigenetic marks