DNA packaging controls access to genetic information
The genetic information in the nucleus is found packaged into nucleosomes for the most part. The position of these structures influences which genes are active and which are not. Scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now been the first to determine the positioning of all nucleosomes in the genome of embryonic stem cells and to compare it with further developed cells. The scientists will investigate whether position changing of nucleosomes is linked to the development of cancer.
Chain of nucleosomes with a protein binding to the linker DNA between two nucleosomes
© Gernot Längst, University of Regensburg
The DNA molecule of a single cell, if stretched out, is a thread of about two meters in length. In order to fit into the nucleus, which is only six micrometers in size, the DNA thread is wrapped around regularly spaced packaging proteins. These structures of DNA and protein are called nucleosomes. The downside of this packaging is that genetic information becomes almost inaccessible in these places and is therefore more difficult to read. The stretches between nucleosomes, however, are free and thus more easily accessible. Hence, the arrangement of nucleosomes tells us a lot about a cell’s genetic program.
The DKFZ Research Group “Genome Organization and Function” led by Associate Professor (PD) Dr. Karsten Rippe has systematically studied the positioning of nucleosomes. Using the most advanced DNA sequencing methods, the group mapped the positioning of all nucleosomes in the genome of embryonic stem cells. For each cell, this amounts to almost 30 million nucleosomes. As expected, they found genetic information that was not needed in a packaged state. By contrast, frequently read genes were usually free of such structures.
The investigators aimed to find out how the arrangement of nucleosomes in embryonic stem cells changes as they further develop into other cell types. Even though the genetic information remains the same in all cells, completely different genes may have to be read depending on a cell’s specialization. To study this question, the group compared embryonic stem cells with cells that were later to develop into skin and brain cells. “To do this, we analyzed about two billion nucleosomes,” Karsten Rippe explains. ”We have found out that the way they are arranged has completely changed in further developed cells. For example, the distance between individual nucleosomes has grown.”
Just how the nucleosomes are shifted back and forth along the DNA is a question which remains to be answered in detail. However, the study shows that this process plays an important role in cell development. Errors occurring in the process might also be responsible for diseases such as cancer. In the German “CancerEpiSys” research network, the scientists are currently studying cancer cells of leukemia patients. One of the goals of this research effort is to produce a nucleosome profile of these cells. The researchers are hoping to draw conclusions about which type of cancer goes along with which changes in the organization of nucleosomes.
The research project was supported by the Federal Ministry of Education and Research (BMBF) as part of the international ERASysBio Program.
Teif, V.B., Vainshtein, Y., Caudron-Herger, M., Mallm, J.-P., Marth, C., Höfer, T. & Rippe, K. Genome-wide nucleosome positioning during embryonic stem cell development. Nature Structural & Molecular Biology, published online 21 October 2012, doi: 10.1038/nsmb.2419
A picture for this press release is available at:
www.dkfz.de/de/presse/pressemitteilungen/2012/images/nucleosome_chain_binding.jpg
Chain of nucleosomes with a protein binding to the linker DNA between two nucleosomes.
Source: Gernot Längst, University of Regensburg
With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.
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