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H. Wang et al., Cell 10.1016 (2018)

Moving DNA to a different part of the nucleus can change how it works

Though the 3 meters of DNA inside the nuclei of our cells looks like a jumbled pile of spaghetti, the genome is, in fact, pretty well organized. Now, scientists have discovered—using a modified version of the gene-editing tool CRISPR—that the location of DNA, not just the order of its base pairs, can make a critical difference in how certain parts of the genome work.

The nucleus is dynamic, with everything—the chromosomes, the nucleolus, and so on—swirling around seemingly randomly. But in the past decade, researchers have realized that DNA on chromosomes inside can reposition itself in specific ways, ways that may alter the activity of the genes being moved. But, until now, they had no good way of proving that hypothesis.

Enter CRISPR: Bioengineers have retooled the gene-editing technique to move specific stretches of DNA from one place to another inside the nucleus itself, they report today in Cell. First, they attach the DNA to a protein that, when prompted by the plant hormone abscisic acid, selectively links up with another protein found only in the target location. The second protein then “snags” the attached DNA, holding it fast in the desired spot. Removing the abscisic acid loosens the connection, freeing the DNA.

Researchers demonstrated that the technique worked by shifting several gene pairs from central locations (above right) to the edge of the nucleus (above left). They also used the technique to move stretches of DNA known as telomeres—the tips of chromosomes implicated in aging. When they moved the telomeres to the inner edge of the nucleus, the cell grew much more slowly, if at all. But when they put telomeres close to cajal bodies, aggregations of proteins and genetic material that process RNA, the cell perked up: It grew faster and divided sooner than usual. Thus, the researchers conclude, the positioning of the telomeres is very important to keeping a cell healthy and productive.

Other researchers say they are impressed with the new CRISPR-GO technique. (GO stands for “genome organization.”) That’s because it opens up a whole new way of altering the organization of the genome, which could pave the way toward a better understanding how the nucleus works and possibly lead to finer control over gene activity to slow aging or prevent disease.