The TET1 enzyme steers us safely through fetal development and fights cancer CELL DEVELOPMENT AND CANCER To ensure normal fetal development and prevent disease, it is crucial that certain genes are on or off in the right time intervals. Researchers in Professor Kristian Helin's group at BRIC and Centre for Epigenetics, University of Copenhagen, have now shown how the TET1 enzyme controls the activity of our genes. The results are published today in the journal Nature. ‐ Our most important finding is that TET1 acts like a safe guard against abnormal growth and development of our cells. TET1 prevents that small molecules, methyl groups, are attached to genes that needs to be active. In this way TET1 ensures that cells can grow and develop normally – and this is crucial for normal fetal development, explains PhD student Kristine Williams. Kristine is together with associate professor Jesper Christensen and PhD student Marianne Terndrup Pedersen the primary forces behind the research results. Whereas the methyl groups ”turn off” the gene by attaching to it, the TET1 enzyme is able to remove the methyl groups and thereby “turn on” the gene. In this way, the TET1 enzyme can fine‐tune gene activity.
Figure 1 In stem cells the TET1 enzyme turns specia‐ lized stem cells genes on by removing methyl groups from the genes. Ill.: Kristine Williams.
Figure 2. In specialized cells, as for example liver cells, TET1 is not present why methyl groups will turn off the stem cell genes. Ill. Kristine Williams.
The results also contribute to our understanding of what goes wrong when normal cells suddenly develop into cancer cells: Our organs and tissues are dependent on constant cellular renewal through cell division, during which a complex
cellular machinery ensures that our DNA is intact and copied correctly. Nonetheless, damage to the DNA, so called mutations, does occur, and this may in worst case result in development of cancer. But here a special type of genes come the body to rescue: the so‐called tumor suppressor genes. Crucial is the ability of the TET1 enzyme to hold the methyl groups in check and thereby letting the tumor suppressor genes exercise their protective function and prevent a cancer to develop. In relation to blood cancer, the gene for another enzyme, TET2 – closely related to TET1 – is frequently mutated. The scientists have reason to believe that TET2, just like TET1, controls the activity by facilitating removal of methyl groups from the DNA and they are currently extending these studies to cellular models for cancer development. The Helin group’s research in the TET enzymes and their function brings us a crucial step closer to an understanding of, how certain types of cancer develops – and this can potentially lead to novel and more targeted therapeutics. Read the abstract and paper in Nature