© koto_feja/Getty ImagesEpigenetic modifications made to both DNA and its cousin, RNA, control gene activity.
Scientists have uncovered a new way that cells control their genes — and it may rewrite our understanding of "epigenetics."
Epigenetics is a form of DNA modification that doesn't affect the DNA sequence itself. Instead, it describes when chemical groups attach to specific genes, thus switching those genes on or off, or else changing the 3D shape of chromosomes.
Now, in a study published Jan. 17 in the journal Cell, scientists have uncovered a whole new method of gene regulation that involves epigenetic tweaks made to both DNA and its molecular cousin RNA, at the same time. Looking forward, the researchers want to unpack how this new type of gene control relates to cancer.
"It is truly exciting to uncover such a new mechanism, further expanding our understanding of gene regulation," Kathrin Plath, director of epigenomics, RNA and gene regulation at UCLA who was not involved in the study, told Live Science in an email.
A new layer of gene regulation
One common type of epigenetic modification is methylation, which describes the addition of a molecule called a methyl group to DNA or histones — proteins that DNA wraps around to become more compact and fit into the nucleus. A protein called DNMT1 adds these molecules to DNA, and its activity can turn gene expression up or down depending on where a given gene is methylated.
In recent years, researchers have also found that RNA — a molecule that shuttles instructions from DNA out into the cell to make proteins — can also be modified. This is mainly done by a protein complex called METTL3-METTL14. This methylation can destabilize the RNA molecule, reducing the amount of protein made.
Every cell in the body uses both RNA and DNA methylation to regulate gene expression. However, it was previously assumed that these processes operated independently. The new study puts that assumption into question.
In the study, the scientists looked at mouse embryonic stem cells and mapped the locations of DNA and RNA methylation as the cells developed. They found that thousands of genes and their complementary RNA molecules contained both methylation markers.
Through additional experiments, the team found that the METTL3-METTL14 complex that interacts with RNA also recruits and physically binds to DNMT1, the protein that tags DNA. This new, bigger complex can then methylate the same gene at the DNA or RNA level. This enables the cell to further fine-tune its gene regulation during cell differentiation — a process by which a stem cell assumes a specific identity, becoming a heart or lung cell, for example.
Previous studies have shown clear connections between DNA and histone modifications, as well as between histone and RNA modifications.
"So why would a cell not also connect an epigenetic modification of DNA and an epigenetic modification of RNA?" said study co-author François Fuks, director of the ULB Cancer Research Center in Belgium. "[Our study shows] the direct connection between DNA methylation and RNA modification that has not been seen before," he told Live Science.
According to Fuks, this study does have some limitations, namely, that it mostly focuses on embryonic stem cell differentiation. DNA and RNA modifications had separately been well characterized in stem cells in past studies, so it made sense for the researchers to start with them. But these same types of DNA and RNA modifications are present in all types of cells. "Seeing this, it's very unlikely that [this mechanism] will be just in ES cells," Fuks said.
This discovery challenges the established view that these RNA- and DNA-modifying processes are completely separate, and it suggests that it may have broader implications in human biology and disease. To that end, Fuks and his team are trying to determine how this new mechanism relates to cancer.
If the coordination of DNA and RNA epigenetics gets thrown off, you may end up with too much or too little of a protein, Fuk suggested. "Now, a key protein will be expressed at a too high level," he said."This could be detrimental for a cell and contribute to tumorigenesis," or the formation of tumors.
There are already approved therapies that inhibit the methylation of DNA, and there's an early-phase clinical trial testing RNA methylation inhibition as a cancer treatment. Fuks and his team are testing the potential of combining these existing therapies to improve patients' outcomes. Preliminary data from their laboratory studies hint this strategy could be useful for patients with leukemia.
At least in petri dishes, "we can revert the cancer progression of leukemic cells by adding these two drugs together," Fuk said. "Eventually, down the line, why couldn't we combine these two drugs to treat patients?"
Reader Comments
Ponder that for a moment.
This is the scientific equivalent to the "magic thinking" of catholics, who believe they have control over a demon when you call his real name. But giving something a scientific-sounding name doesn't explain anything.
The ancient Greek "Epi" means "outside" - thus epigenetics is something "not within genetics".
But if (according to Darwinists) we are controlled by our genes, and our genes are modified by "epigenetics", i.e. something outside, what then - and what does that mean ?
The typical circular reasoning of "contemporary science", hidden behind foreing lingo terms ...
Adopted children take on the diseasesof the host family, showing an example of how it's 'the environment' just like Lamarck stated. Lipton went on to reveal that besides the water we drink, the food we eat and the air we breathe ....our environment is also the thoughts we think, the people we surround ourselves with, our beliefs, our desires, self sabotage, etc.
Through Bruce's work, he removed the nucleus of the cell thinking that was the brain and it continued to survive. He later on figured out the brain of the cell was the Membrane around it. As it decided what to let IN and what to keep OUT. He then began calling it the Membrain.
As with us.....what do we let in and what do we keep out! Have a ponder! Hopefully, you all are letting in the good stuff!
Great book, just put out the 10 year anniversary addition.
Excellent point. Interestingly, earlier today, I found myself wondering about the young people I know, and how they are having trouble finding and keeping life partners. It made me wonder if, somewhere in the biomedical or mental health research, there might be some who are trying to interrupt natural human emotions to make placid zombies, who cannot relate to others.
Here is a Brave AI response:
"The environment plays a crucial role in epigenetics and gene expression through various mechanisms. Environmental factors can alter gene expression without changing the DNA sequence itself, leading to changes in the epigenome. These changes can be influenced by physical and psychological factors, including stress, diet, and exposure to pollutants.
For instance, heavy metals such as methylmercury, arsenic, and cadmium can disrupt epigenetic function, altering gene expression and increasing the risk for poor birth outcomes, developmental abnormalities, cancer, and neurodegeneration. Similarly, chronic stress can alter epigenetic markers in the brain, making individuals more responsive to stressful stimuli and increasing the risk for behavior changes, cardiovascular disease, and other health issues."
The critical question is - how come "epigenetics" exist in the first place ?
It seems like like our genes are a super-set of certain genetic expressions, and in response to environmental influences, sets get activated or deactivated. As if "someone" has planned and implemented features for a wide range of environments ...
Or can anybody point me to a plausible Darwinian explanation ? I think there is none, mal-adapted species have to die out according to their orthodoxy ...