Spatial Rules Governing the Shape of DNA Explained

A new study—published in Genome Biology—reports that the three-dimensional structure of DNA is determined by a series of spatial rules based on particular protein sequences and their order. 

 "Our study's greatest innovation lies in having identified precise rules for the disposition of CTCF proteins,” says Luca Nanni, first author of the study. “The beauty and simplicity of CTCF's grammar show us how nature and evolution produce regularity and incredibly ingenious and functional systems."  

Topological domains are crucial to the study of the three-dimensional structure of DNA. By understanding these domains, scientists get a closer look at the mechanisms with which DNA wraps itself through a complex system that maintains accessibility and allows for correct reading to take place inside the cell’s nucleus. 

"Knowing these rules allow CTCF sequences to be engineered to obtain the desired DNA three-dimensional structure. For example, it should be possible to make two disconnected genes interact. Molding DNA structure will open doors to the creation of pharmaceuticals for the treatment of diseases such as cancer," Nanni adds. 

The research team from Politecnico di Milano focused on specific DNA sequences that encode for the CTCF protein. "This protein isolates portions of DNA creating barriers between the various topological domains. With the help of computer simulations and the creation of a model for classifying these proteins according to their orientation, we identified a surprising regularity in their arrangement along the DNA sequence," he says. 

Their findings also report that the orientation and order of these DNA sequences make it possible to reconstruct the topological domains.