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Methods Mol Biol. 2018;1767:65-87. doi: 10.1007/978-1-4939-7774-1_3.

Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.

Author information

1
Chemical and Biomolecular Engineering Department, North Carolina State University, Raleigh, NC, USA.
2
Chemical and Biomolecular Engineering Department, North Carolina State University, Raleigh, NC, USA. ajkeung@ncsu.edu.
3
W. M. Keck Center for Behavioral Biology, Genetics Program, North Carolina State University, Raleigh, NC, USA. ajkeung@ncsu.edu.

Abstract

The advent of locus-specific protein recruitment technologies has enabled a new class of studies in chromatin biology. Epigenome editors enable biochemical modifications of chromatin at almost any specific endogenous locus. Their locus specificity unlocks unique information including the functional roles of distinct modifications at specific genomic loci. Given the growing interest in using these tools for biological and translational studies, there are many specific design considerations depending on the scientific question or clinical need. Here we present and discuss important design considerations and challenges regarding the biochemical and locus specificities of epigenome editors. These include how to account for the complex biochemical diversity of chromatin; control for potential interdependency of epigenome editors and their resultant modifications; avoid sequestration effects; quantify the locus specificity of epigenome editors; and improve locus specificity by considering concentration, affinity, avidity, and sequestration effects.

KEYWORDS:

Biochemical specificity; CRISPR; Chromatin modifiers; DNA-binding domain; Epigenome engineering; Locus specificity; Transcription activator-like effectors; Zinc finger proteins

PMID:
29524129
PMCID:
PMC5972380
DOI:
10.1007/978-1-4939-7774-1_3
[Indexed for MEDLINE]
Free PMC Article

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