With the help of a new rendition of CRISPR-Cas9 gene editing technology, scientists at Stanford have shown that it's possible to shuttle pieces of DNA around in the nucleus, affecting gene expression and cell behavior.
The study, led by Stanley Qi, PhD, hinges on a reengineered version of CRISPR called "CRISPR-genome organization" or CRISPR-GO, which can physically relocate targeted pieces of DNA.
As reported by our release:
In the proof-of-principle study, Qi investigated three distinct subregions of the nucleus using CRISPR-GO, testing an overarching hypothesis: Do genes and other genetic elements behave differently in different zones of the nucleus?
So far, their data show that specific compartments and some free-floating bodies of proteins in the nucleus can sway the function of repositioned DNA. Depending on where the genetic materials are located, some nuclear regions repress gene expression and some accelerate telomere growth, and subsequently cell division. One protein body may even hold the power to suppress tumor formation.
The research is published in Cell.
DNA is often though of as a list of As, Cs, Ts and Gs, written as a string of letters that codes for a range of biology's fundamental elements. But magnified from its microscopic state, this script would appear a long, winding strand of three-dimensional rope.
Inside a cell, this molecular twine bundles up in a central compartment that acts as the control center, called the nucleus. But it's not just crammed in haphazardly, the physical location of DNA in the cell matters. Qi explains in our release:
The question of why spatial organization in a cell matters is an important one, and it’s also not one that scientists agree on... CRISPR-GO could provide an opportunity to answer that question by enabling us to target, move and relocate very specific stretches of DNA, and see how their new placements in the nucleus change how they function.
As I explain in the release, CRISPR-GO connects, like the tracks of a toy train, two regions of the nucleus: the target DNA's original location and its future destination.
Qi says that in the future, they hope to understand why different locations in the nucleus can sway the function of DNA so drastically, with the intention to one day use that information to enhance human health.
Photo by Dan Paul