New insight as to how cells maintain their identity
In the body's cells, certain proteins are of vital importance to know which genes are active or deactivated. Today, researchers at the University of Copenhagen and the Memorial Sloan Kettering Cancer Center have discovered which proteins are needed to maintain adequate genetic regulation.
All the more than 200 different cell types in our body contain the same DNA. Which of these genes that are expressed determines each cell type. It is therefore essential that gene activity be controlled with great precision.
Thus, a stem cell can transform into anything from skin to bone cell, depending on which parts of the genome are expressed.
Researchers in Professor Kristian Helin's research group have been working for several years to understand the mechanisms that control whether a gene is active or inactive. This research is crucial to understanding how cells specialize and maintain their identity, their normal embryonic development and how various diseases can develop.
In a new study, researchers at the Biotech Research & Innovation Center (BRIC) and the Novo Nordisk Foundation Center for Stem Cell Biology (DanStem) at the University of Copenhagen and the Memorial Sloan Kettering Cancer Center in New York have obtained crucial new results.
The results were recently published in the scientific journal Molecular Cell and provide an overview of how epigenetic mechanisms control gene activity.
"In addition, the results could have an impact on the future treatment of some cancers related to the protein complex studied, including lymphoma, leukemia and a particular type of brain cancer often seen in children," says Kristian Helin, BRIC Professor and Director of Research at the Memorial Sloan Kettering Cancer Center.
One of the main protein complexes that regulates whether genes are activated or deactivated is called PRC2. To ensure that the complex binds to the right places in the genome, a number of other proteins are associated with PRC2.
In the recently published article, the research group studied the importance of six different proteins associated with PRC2, and the group showed that the six proteins help to direct PRC2 to the right place in the genome.
In 15 different combinations, the researchers removed the proteins associated with embryonic stem cells one by one. Thus, the researchers were able to study the contribution of each protein to the activity and binding of the PRC2 complex to specific areas. It was found that the ability to find the right place in the genome remained intact until the six associated proteins were removed from the stem cells.
This result surprised the researchers, according to the study's main author, Jonas Højfeldt, postdoc:
"We assumed that each of the associated proteins was responsible for its own area to which the PRC2 complex was to be guided. Instead, we have seen that they have all contributed to the places where the complex connects. As long as only one of the associated proteins remained, the capacity remained intact," he says.
