Abstract
Genome targeting has quickly developed as one of the most promising fields in science. By using programmable DNA-binding platforms and nucleases, scientists are now able to accurately edit the genome. These DNA-binding tools have recently also been applied to engineer the epigenome for gene expression modulation. Such epigenetic editing constructs have firmly demonstrated the causal role of epigenetics in instructing gene expression. Another focus of epigenome engineering is to understand the order of events of chromatin remodeling in gene expression regulation. Groundbreaking approaches in this field are beginning to yield novel insights into the function of individual chromatin marks in the context of maintaining cellular phenotype and regulating transient gene expression changes. This review focuses on recent advances in the field of epigenetic editing and highlights its promise for sustained gene expression reprogramming.
Highlights
Epigenetics is the study of heritable yet reversible changes in gene expression, which are independent of the underlying DNA sequence
This review focuses on recent advances in the field of epigenetic editing and highlights its promise for sustained gene expression reprogramming
It recruits several factors linked to increased chromatin accessibility and the deposition of active histone marks, such as acetylation of the lysine 27 residue of histone subunit 3 (H3K27ac) [48, 49]. Another activator exploited for targeted gene activation is the p65 subunit of the human NF-jB complex, which has been coupled to zinc finger proteins (ZFPs) [50], Transcription-Activator-Like Effector (TALE) [51, 52], and deactivated Cas9 (dCas9) [53]
Summary
Epigenetics is the study of heritable yet reversible changes in gene expression, which are independent of the underlying DNA sequence. To maintaining mitotically stable expression patterns, chromatin controls DNA accessibility through, for instance, post-translational modifications (PTM) of the histone tails or modification on the DNA such as methylation [4] These modifications can directly or indirectly influence chromatin structure by modulating DNA–histone interactions and form docking sites to facilitate recruitment of proteins to the chromatin [5]. It is feasible to target epigenetic effector domains to any given genomic locus The goal of such epigenetic editing is to rewrite an epigenetic mark at any locus at will, and eventually modulate the expression of endogenous genes. We summarize recent epigenetic editing reports using different DNA-binding platforms and several activators, repressors, or epigenetic enzymes targeted to endogenous loci
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