CRISPR-Mediated Programmable 3D Genome Positioning and Nuclear Organization.
PMID:30318144
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IF: 66.850
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Cited by: 146
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Abstract

Programmable control of spatial genome organization is a powerful approach for studying how nuclear structure affects gene regulation and cellular function. Here, we develop a versatile CRISPR-genome organization (CRISPR-GO) system that can efficiently control the spatial positioning of genomic loci relative to specific nuclear compartments, including the nuclear periphery, Cajal bodies, and promyelocytic leukemia (PML) bodies. CRISPR-GO is chemically inducible and reversible, enabling interrogation of real-time dynamics of chromatin interactions with nuclear compartments in living cells. Inducible repositioning of genomic loci to the nuclear periphery allows for dissection of mitosis-dependent and -independent relocalization events and also for interrogation of the relationship between gene position and gene expression. CRISPR-GO mediates rapid de novo formation of Cajal bodies at desired chromatin loci and causes significant repression of endogenous gene expression over long distances (30-600 kb). The CRISPR-GO system offers a programmable platform to investigate large-scale spatial genome organization and function.

Keywords

3D-FISH
Spatial Genomics
3D genome
CRISPR
CRISPR-GO
Cajal body
Cas9
PML body
gene regulation
gene repression
nuclear body
nuclear periphery

MeSH terms

Abscisic Acid
CRISPR-Cas Systems
Cell Line, Tumor
Chromatin
Coiled Bodies
Gene Editing
Gene Expression Regulation
Genetic Loci
Genome
Humans
In Situ Hybridization, Fluorescence
S Phase Cell Cycle Checkpoints

Authors

Wang, Haifeng
Xu, Xiaoshu
Nguyen, Cindy M
Liu, Yanxia
Gao, Yuchen
Lin, Xueqiu
Daley, Timothy
Kipniss, Nathan H
La Russa, Marie
Qi, Lei S

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