Grammar for DNA 3D Structure
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‘Grammar’ for DNA 3D Structure

A study recently published by Luca Nanni, a Ph.D. student in Computer Science and Engineering at Politecnico di Milano in Genome Biology, says a series of spatial rules based on particular protein sequences and their order can determine the three-dimensional structure of DNA. Colin Logie, professor at the University of Nijmegen, and Stefano Ceri at Politecnico di Milano co-led the study.

Researchers identified precise rules for the disposition of CTCF proteins, which is the study’s greatest innovation. How nature and evolution produce regularity and incredibly ingenious and functional systems is shown by the beauty and simplicity of CTCF’s grammar. CTCF sequences can be engineered, and the desired DNA three-dimensional structure can be obtained with the knowledge of these rules. For example, making two disconnected genes interact should be possible with the help of CTCF’s grammar. The first author of the study, Luca Nanni, said, molding DNA structure will pave the way for the development of therapeutics for the treatment of cancer-like diseases.

To wrap itself, the two meters long unrolled DNA requires a complex system that maintains its correct reading and accessibility to reside in the nucleus of a cell. Topological domains, which are thought to aggregate

DNA zones with similar roles and behavior, is crucial in the study of the three-dimensional structure of the genome. For example, genes with similar functions are more probable to reside in the same topological domain. The researchers focused on specific DNA sequences that code for CTCF protein. Regions of DNA generating barriers between the various topological domains are isolated by this protein. They identified a surprising regularity in their arrangement along the DNA sequence with the help of computer simulations and the creation of a model for classifying these proteins according to their orientation.