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CRISPR-Mediated Programmable 3D Genome Positioning and Nuclear Organization.


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.

SUBMITTER: Wang H 

PROVIDER: S-EPMC6239909 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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CRISPR-Mediated Programmable 3D Genome Positioning and Nuclear Organization.

Wang Haifeng H   Xu Xiaoshu X   Nguyen Cindy M CM   Liu Yanxia Y   Gao Yuchen Y   Lin Xueqiu X   Daley Timothy T   Kipniss Nathan H NH   La Russa Marie M   Qi Lei S LS  

Cell 20181011 5


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 interroga  ...[more]

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