A new tool to study complex genome interactions

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Researchers at the Berlin Institute of Medical Systems Biology of the Max Delbrück Center (MDC-BIMSB) have developed a technique called Genome Architecture Mapping (“GAM”) to peer into the genome and see it in glorious technicolor. GAM reveals information about the genome’s spatial architecture that is invisible to scientists using solely Hi-C, a workhorse tool developed in 2009 to study DNA interactions, reports a new study in Nature Methods by the Pombo lab.

GAM provides more complex information

Techniques such as Hi-C and GAM allow scientists to freeze and study the interactions between regulatory sequences and genes. In Hi-C, chromatin is cut into pieces using enzymes and then glued together again in such a way that two-way DNA interactions are revealed upon sequencing. In GAM, first described by the Pombo team in Nature in 2017, scientists take hundreds of thin slices of nuclei, each from individual cells, and extract DNA from them. They sequence the DNA and statistically analyze the data to learn which regions interact.

Using this technique, the team created a map of the three-dimensional interactions. When they compared this with existing 3D maps of the genome created using Hi-C, they found many novel interactions. This puzzled them until they realized they were seeing more complex interactions using GAM, with multiple regions of DNA coming together at the same time. “These more complex contacts contain active genes, regulatory regions, and super enhancers, which regulate important genes that determine cell identity,” says Dr. Christoph Thieme.

By Max Delbrück Center for Molecular Medicine

Article can be accessed on: phys.org