We begin our lives as a single cell. This divided into billions of cells which acquired specific jobs, such as communication in the brain and contraction in the muscles. However, the DNA sequence remains identical in each of our cells. How do cells, which all contain the same DNA sequence, accomplish such varied tasks?
So far, we have understood that specialized cells (like brain and muscle cells) differ from each other based on the genes they express. In other words, if all cells contain the same genes, only a fraction of those genes are “turned on” in a given cell type. Research into “epi”genetics has shown that DNA and the proteins it is wrapped around are decorated with modifications that determine whether a gene is turned on or off, without changing the DNA sequence itself. Not only is epigenetics important for transforming a simple cell into an organism with complex tasks, but in cancer cells the epigenome is disrupted.
Using stem cells to model epigenetic reprogramming
In an article published in Nature Structural and Molecular Biologyscientists simulated the early stages of embryonic development in mice in the laboratory in order to study the effect of establishing epigenetic modifications in the embryo. They discovered that two epigenetic modifications that individually repress gene activation can meet and cancel each other out, thus non-intuitively conferring gene activation. They found many genes affected by this process.
Manipulating the epigenome to demonstrate the function of DNA methylation
Additionally, they used various cutting-edge techniques, including epigenome editing using a CRISPR/Cas9 system to precisely modify DNA methylation marks at genes of interest. These tools allowed them to validate their results, which help to explain how certain genes are naturally activated during development. Interestingly, epigenetic modifications established during development are inherited into adulthood, providing information about whether genes are turned on or off throughout life. Overall, this research deepens our understanding of the interplay between two mechanisms responsible for gene silencing, with important implications for several cancers where these two pathways are dysregulated.
