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Cell. 2018 Nov 15;175(5):1405-1417.e14. doi: 10.1016/j.cell.2018.09.013. Epub 2018 Oct 11.

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

Author information

1
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
2
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Cancer Biology Program, Stanford University, Stanford, CA 94305, USA.
3
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Statistics, Stanford University, Stanford, CA 94305, USA.
4
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA; Stanford ChEM-H, Stanford University, Stanford, CA 94305, USA. Electronic address: stanley.qi@stanford.edu.

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 genome; CRISPR; CRISPR-GO; Cajal body; Cas9; PML body; gene regulation; gene repression; nuclear body; nuclear periphery

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PMID:
30318144
PMCID:
PMC6239909
DOI:
10.1016/j.cell.2018.09.013
[Indexed for MEDLINE]
Free PMC Article

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