Mechanistic role of DNA changes detected during differentiation

Research at the Max Planck Institute of Psychiatry provides a better understanding of epigenetic changes

April 24, 2018

Some genes become active, some do not. This has to do with so-called epigenetic mechanisms. One of the most important epigenetic mechanisms is DNA methylation. Previous studies have only been able to give limited inferences as to whether such DNA changes are the cause or consequence of other processes. The Max Planck Institute of Psychiatry (MPI), together with its collaborators, has now been able to show the effects DNA methylation can have on the functional level. This is important in order to better understand the regulation of developmental processes by epigenetic changes. The results have now been published in the prestigious journal Cell Stem Cell.

Scientists at the MPI and their colleagues at Northwestern University in Chicago and the Max Planck Institute for Molecular Genetics in Berlin turned pluripotent stem cells into motor nerve cells, which are found in the spinal cord. During this differentiation process, they switched off the cells ability to form new DNA methylation patterns to find out more about the mechanistic role. They used a variety of technologies that allowed them to draw conclusions about the epigenetic state and showed which cells were active and which were not.

They discovered a shift in cell types produced during the differentiation phase: far fewer motor neurons formed when the cells’ DNA methylation was switched off and instead other types of cells were produced. Scientists were able to associate this change in cell type and physiology with altered DNA methylation patterns at specific sites in the genome. Furthermore, they were able to demonstrate the causality of these specific changes observed using specific modification experiments based on epigenome editing.

This demonstrated the causal relationship between DNA methylation changes and altered cell development. "If there are changes in the DNA methylation pattern in specific parts of the genome, this has an impact on the identity of the generated cells," says lead author Michael Ziller from the MPI.

The question that now arises is what changes are relevant, because not all of them have consequences on the formation of new cells. The study presents strategies on how to get more results on this in the future.


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