
The physical organization of the genome plays a central role in biological processes ranging from cell division to gene regulation. Understanding the functional significance of genome spatial organization is currently hampered, however, by the lack of tools to systematically perturb genome structure in space and time. We are developing new approaches to address this challenge. To physically reposition genes, we use programmable CRISPR-Cas DNA binding domains tethered to targeting domains that localize to specific subnuclear sites. We have successfully recruited genes to the nuclear periphery and nuclear pore complex (NPC) in yeast, and we observe transcriptional activation when genes are recruited to the NPC. This approach will allow us to address basic mechanistic questions about how genes respond to spatial repositioning and how the physical structure of the genome contributes to gene regulation.

The physical organization of the genome plays a central role in biological processes ranging from cell division to gene regulation. Understanding the functional significance of genome spatial organization is currently hampered, however, by the lack of tools to systematically perturb genome structure in space and time. We are developing new approaches to address this challenge. To physically reposition genes, we use programmable CRISPR-Cas DNA binding domains tethered to targeting domains that localize to specific subnuclear sites. We have successfully recruited genes to the nuclear periphery and nuclear pore complex (NPC) in yeast, and we observe transcriptional activation when genes are recruited to the NPC. This approach will allow us to address basic mechanistic questions about how genes respond to spatial repositioning and how the physical structure of the genome contributes to gene regulation.