3 April 2020

Researchers Discover How the Genes 'Start up' in the Beginning of Life

Pregnancy

A particular enzyme plays a special role when the genetic machinery has to be started at the very first stage of life: as a single cell after fertilisation. This is shown in a new study from the University of Copenhagen, (ICMM and BRIC/DanStem)). The researchers believe that the new knowledge may offer an explanation as to why some fertilisations fail.

By Sund Press Officer: Mathias Traczyk
93 56 58 35
mathias.traczyk@sund.ku.dk

IVF Treatment

All people start life as a single cell. After a sperm cell has fertilised the egg of the mother, a wealth of processes must be initiated in order for a cell to become a whole human being.

However, this development may sometimes go awry, both in connection with natural fertilisation and when people get help from a fertility clinic. Therefore, researchers are constantly trying to gain more knowledge about what happens in the very early development.

Now, researchers from the University of Copenhagen led by Eva Hoffmann@ICMM and Kristian Helin@Bric/DanStem have gained new insights into the factors that drive the genetic processes at the beginning of life. In a new study published in the scientific journal Nature Cell Biology, they have found a specific enzyme that seems to control whether the development starts properly.

’You could envision the DNA strand in the very first cell as a large landscape. On it, some runways have been marked which show the way for other molecules and indicate which genes need to start first. We have now found an enzyme that keeps the runways open. In other words, the enzyme ensures that the fetal development can start in a proper and healthy manner’, explains Eva Hoffmann, Professor at the Department of Cellular and Molecular Medicine.

Tightly Packed DNA

In the new study, the researchers have mapped the presence and activity of the enzyme in both human eggs and mice. They have also investigated the significance of deactivating the enzyme in mice.

‘In order for a fetus to develop in a healthy manner, the cells need to be able to divide. But in our study, we can see that the cell division does not start properly if the enzyme has been deactivated. The right gene programmes will not be turned on. And that means that the fertilised egg never develops into more than four cells before they are lost’, says Eva Hoffmann.

Keeping the runways open is about the way DNA physically looks inside the cell. The reason being that the biological processes in the cells are dependent on the availability of the genes.

‘Once the sperm cell has fertilised the egg, the DNA is packed very tightly. If the enzyme is not there to open the runway, it is inaccessible to outside molecules. This means that the right gene programmes cannot be switched on and started’, explains Eva Hoffmann.

The researchers embarked on the research project because they wanted to find an explanation as to why a large proportion of fertilisations goes wrong already in the petri dish. It is their hope that the new result can be used in fertility clinics in the long term.

'The field of reproductive health in the context of safeguarding fertility outcomes will (or already is) in my opinion, be a major global health challenge for the planet along with infectious diseases and metabolism disorders. And there is much to do. I believe that this study could achieve its full potential due to the excellent collaboration of expertise on display between the Hoffmann (human germline; ICMM-CCS), Helin (epigenetics and chromatin; Danstem/BRIC/MSKCC), Dahl (low-input chromatin mapping; Oslo) laboratories and Mads Lerdrup (BRIC/ICMM-CCS). I am in particular thankful for the immensely rewarding opportunity to lead and drive such a study from start to finish.'- says first author Aditya Sankar. 

Read the entire study: ‘KDM4A regulates the maternal-to-zygotic transition by protecting broad H3K4me3 domains from H3K9me3 invasion in oocytes’