Epigenetic changes that occur in both DNA and its RNA counterpart regulate genetic activity. (Image credit: koto_feja/Getty Images)
Researchers have discovered a new way cells control their genes that could change the way we think about 'epigenetics'.
Epigenetics is a type of DNA modification that does not affect the DNA sequence itself. Instead, it explains how chemical groups attach to specific genes, turning them on or off, and changing the three-dimensional structure of chromosomes.
In a study published January 17 in the journal Cell, scientists presented an entirely new method of gene regulation that involves epigenetic changes occurring simultaneously in both DNA and its molecular equivalent, RNA.
Looking to the future, researchers are keen to understand how this new type of gene control might be linked to cancer.
“This is really an exciting discovery of a new mechanism that further advances our understanding of gene regulation,” Catherine Plath, director of epigenomics, RNA, and gene regulation at the University of California, Los Angeles, who was not involved in the study, told Live Science in an email.
New level of gene regulation
One of the most common types of epigenetic modification is methylation, which refers to the addition of a molecule known as a methyl group to DNA or histones, proteins that wrap DNA to make it compact and fit into the nucleus. A protein called DNMT1 adds these molecules to DNA, and its activity can increase or decrease gene expression depending on the location of the methylation of a particular gene.
In recent years, scientists have also discovered that RNA, the molecule that carries instructions from DNA to the cell to make proteins, can also be modified. This is typically done by a protein complex called METTL3-METTL14. This methylation can destabilize the RNA molecule, reducing the amount of protein produced.
Every cell in the body uses both RNA methylation and DNA methylation to control gene expression. However, it was previously thought that these processes acted independently. A new study challenges this assumption.
In the study, the scientists analyzed mouse embryonic stem cells and mapped DNA and RNA methylation sites at different stages of cell development. They found that thousands of genes and their complementary RNA molecules contained both methylation markers.
In additional experiments, the team discovered that the METTL3-METTL14 complex that interacts with RNA also recruits and physically binds to DNMT1, a protein that tags DNA. This new, larger complex can then methylate the same gene at both the DNA and RNA levels. This allows the cell to further fine-tune gene regulation during cellular differentiation, the process by which a stem cell acquires a specific identity, becoming, for example, a heart or lung cell.
Previous studies have shown a clear link between DNA and histone modifications, as well as between histone and RNA modifications.
“So why can’t a cell also combine epigenetic DNA modification and RNA modification?” said study co-author Francois Fuchs, director of the ULB Cancer Research Center in Belgium. “[Our study demonstrates] a direct link between DNA methylation and RNA modification that has not been seen before,” he told Live Science.
The study has some limitations, Fuchs said, namely that it focused primarily on the differentiation of embryonic stem cells. DNA and RNA modifications have been separately well characterized in stem cells in previous studies, so it made sense for the researchers to start there. But the same types of DNA modifications
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