Scientists have discovered a new way in which cells control their genes, and can rewrite our understanding of “epigenetics.”
Epigenetics It is a form of DNA modification that does not affect the DNA sequence itself. On the other hand, it describes when chemical groups bind to specific genes, extinguishing or deactivating those genes, or changing the 3D form of chromosomes.
Now, in a study published on January 17 in the magazine CellScientists have discovered a completely new method of gene regulation that involves epigenetic adjustments made for both DNA and molecular cousin RNAat the same time.
Looking towards the future, researchers want to unpack how this new type of gene control is related to cancer.
“It is really exciting to discover such a new mechanism, further expanding our understanding of gene regulation.” Kathrin PathDirector of Epigenomics, RNA and gene regulation of UCLA who did not participate in the study, said Live Science in an email.
Related: The sperm cells carry traces of child stress, the epigenetic study finds
A new gene regulation layer
A common type of Epigenetic modification It is methylation, which describes the addition of a molecule called Methyl group To DNA or histones: proteins that DNA is involved to be more compact and fit into the nucleus. A protein called DNMT1 Add these molecules to the DNA, and your activity can convert gene expression up or down depending on where a given gene is getting to get.
In recent years, researchers I have also found that RNA – You can also modify a molecule that draws the DNA instructions to the cell to make protein. This is done mainly by a protein complex called Mettl3-Mettl14. This methylation can destabilize the RNA molecule, reducing the amount of protein made.
Each body cell uses RNA and DNA methylation to regulate gene expression. However, it was previously supposed that these processes worked independently. The new study questions that assumption.
In the study, the scientists observed the embryonic mouse stem cells and map the locations of the methylation of DNA and RNA as the cells developed. They discovered that thousands of genes and their complementary RNA molecules contained both methylation markers.
Through additional experiments, the team found that the mettl3-methtl14 complex that interacts with RNA also recruits and physically binds to DNMT1, the protein that label the DNA. This new and largest complex can put the same gene at DNA or RNA level. This allows the cell to further adjust its gene regulation during cell differentiation, a process by which a stem cell assumes a specific identity, becoming a heart or pulmonary cell, for example.
Previous studies have demonstrated clear connections between DNA and histone modificationsas well as between Histon and RNA modifications.
“So why would a cell also connect an epigenetic modification of DNA and an epigenetic modification of RNA?” Said Co -author of the study François FuksDirector of the ULB Cancer Research Center in Belgium. “[Our study shows] The direct connection between DNA methylation and the modification of RNA that had not been seen before, “he told Live Science.
According to Fuks, this study has some limitations, namely, which focuses mainly on the differentiation of embryonic stem cells. DNA and RNA modifications had been characterized separately in stem cells in previous studies, so it made sense for researchers to begin with them. But these same types of DNA and RNA modifications are present in all types of cells.
“Seeing this, it is very unlikely that [this mechanism] It will be alone in cells, “said Fuks.
This discovery challenges the established opinion that these modifying RNA and DNA processes are completely separated, and suggests that it can have broader implications in biology and human disease. To that end, Fuks and his team are trying to determine how this new mechanism is related to cancer.
If the coordination of the DNA and RNA epigenetics is eliminated, it can end with too much or very little protein, Fuk suggested. “Now, a key protein will be expressed at a level too high,” he said. “This could be harmful to a cell and contribute to tumorigenesis,” or tumor formation.
There are already approved therapies that inhibit DNA methylation, and there is a Early phase clinical trial RNA methylation inhibition test as cancer treatment. Fuks and his team are testing the potential to combine these existing therapies to improve the results of patients. The preliminary data of their laboratory studies suggest that this strategy could be useful for patients with leukemia.
At least in Petri dishes, “we can reverse the progression of leukemic cell cancer by adding these two medications together,” said Fuk. “Finally, in the future, why could we not combine these two medications to treat patients?”
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