Engineering of Effector Domains for Targeted DNA Methylation with Reduced Off-Target Effects.

ABSTRACT: Epigenome editing is a promising technology, potentially allowing the stable reprogramming of gene expression profiles without alteration of the DNA sequence. Targeted DNA methylation has been successfully documented by many groups for silencing selected genes, but recent publications have raised concerns regarding its specificity. In the current work, we developed new EpiEditors for programmable DNA methylation in cells with a high efficiency and improved specificity. First, we demonstrated that the catalytically deactivated Cas9 protein (dCas9)-SunTag scaffold, which has been used earlier for signal amplification, can be combined with the DNMT3A-DNMT3L single-chain effector domain, allowing for a strong methylation at the target genomic locus. We demonstrated that off-target activity of

SUBMITTER: Hofacker D 

PROVIDER: S-EPMC7013458 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature