CRISPR-Mediated Programmable 3D Genome Positioning and Nuclear Organization

• Haifeng Wang ^[1] ; Xiaoshu Xu ^[1] ; Cindy M. Nguyen ^[1]
  1. [1] Stanford University

     Stanford University

     Estados Unidos

     
• Localización: Cell, ISSN 0092-8674, Vol. 175, Nº. 5, 2018, págs. 1405-1417
• Idioma: inglés
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• Resumen

  • 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.