Exploring the packaging code for DNA

New work by the MPI-IE Bioinformatics Unit helps to understand how DNA is packed and organized

The common picture of DNA is that of a spiral staircase. This huge 2 meter long molecule contains all our genetic information and is flexibly folded up and packed to fit within the tiny nucleus of every cell. It is well known that errors in the DNA sequence can result in various diseases, but scientists are only just starting to understand how the precise packaging of DNA may also affect cellular function and our health.

At the first glance, folded and compressed DNA seems to form a tangled spaghetti-like structure. But actually it is strictly organized in substructures and clustered domains. Although their functions are not fully understood yet, it has been shown that changes at the boundaries of these domains, can lead to significant disruptions in gene regulation and cause associated diseases.

To better understand how these domains are formed, scientists from the Bioinformatics Unit of the Max Planck Institute of Immunobiology and Epigenetics in Freiburg (MPI-IE) released new data and powerful software, called HiCExplorer, that increases the resolution at which the three-dimensional organization of DNA can be studied. “It is like having a more powerful microscope. Our software allows us to zoom into the regions that separate domains and to identify tiniest DNA patterns,” explains Fidel Ramirez, first author of the newest study.

HiCExplorer – a Microscope for DNA written in Software

Using their new methods, the team was not only able to detect novel sequence signals, but also identified potential proteins that recognize such sequences and help establishing domain boundaries. However, DNA sequence contains features that can guide structure and organization of its own packaging. “Our results suggest a new three-dimensional code, written in the DNA alphabet, that we are just beginning to understand,” says Fidel Ramirez.

All results have been collected in a comprehensive data archive with large data sets for the human, mouse and fly genome. It can be freely accessed and visualized from all over the world: Chorogenome Navigator. “Clearly this is only the beginning”, says Thomas Manke, head of the MPI-IE Bioinformatics Unit, “but our tools and data will help researchers to conduct follow-up studies and develop a better understanding of how the complex information in our DNA is organized and regulated.”