期刊
CELL
卷 175, 期 5, 页码 1405-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2018.09.013
关键词
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资金
- Pew Scholar Program
- Alfred P. Sloan Foundation
- NIH Director's Early Independence Award [OD017887]
- NIH 4D Nucleome Imaging Tool U01 [EB021240]
- Li Ka Shing Foundation
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 relocalication 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 CRISPRGO system offers a programmable platform to investigate large-scale spatial genome organization and function.
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