Stretched end to end, the DNA in the nucleus of just one of your cells would be as long as you are. Now, using sophisticated statistics, imaging, and experimental data, biophysicists have a clearer idea about how all this genetic material is squished into such a tiny space.
"This new work does reveal a striking, high-resolution model of the human genome," says Job Dekker, a biologist at the University of Massachusetts Medical School in Worcester, who was not involved with the work. "It is indeed beautiful."
Over the past decade, researchers have come to realize that how our DNA is bunched into the nucleus is a miracle of packaging, with very deliberate loops and bends that bring specific parts of each chromosome into contact to help control what genes are active. "Cells have been evolving to exploit this apparently chaotic organization to efficiently store the genetic information and use it for their function," says Marco Di Stefano, a biophysicist now at the National Centre for Genomic Analysis in Barcelona, Spain.
In the new study, he and his colleagues used statistical approaches to convert experimental data into a 3D model. Previous experiments—capturing when one bit of DNA came close to another bit of DNA—had provided only indirect information about individual connections, but the new modeling resulted in a comprehensive, biologically correct depiction (visualized above) of how our DNA fits into a nucleus. In the video, each chromosome is a different color. The model incorporated imaging data with the experimental results about DNA contacts. The analysis yielded specifics not discernable from the experimental data alone, such as showing that active genes are near the center of the nucleus and inactive ones are toward the edges, the team reports this month in Scientific Reports.
The model is "summarizing a large portion of the knowledge we have on the DNA organization in the nucleus," says Di Stefano, who did the work while a graduate student at the International School for Advanced Studies in Trieste, Italy. He hopes to next build a model that can change over time, as "with our approach, it is possible to study the dynamics of the genome” as cells adjust to changing conditions by altering the DNA’s 3D structure to turn different genes on and off. But already, this model gives researchers a better sense of how chromosomes are organized, a useful insight for both basic and biomedical research, Dekker says.