Recent research reveals that DNA and RNA epigenetics, previously studied as independent systems, actually function as a complementary regulatory network. This dual mechanism enables precise gene activation, critical for cellular development and function. Published in Cell, the study uncovers a novel mode of gene regulation and its role in diseases like cancer, paving the way for personalized therapies using “epigenetic drugs” that target both DNA and RNA.
A study reveals DNA and RNA epigenetics
work together as a complementary system for precise gene regulation, crucial
for cell function and development, with implications for advanced cancer
therapies.
Our genes carry the complete set of
instructions necessary for our body to function, but their expression must be
carefully regulated to ensure that each cell fulfills its specific role
efficiently. This is where DNA and RNA epigenetics come into play: a collection
of mechanisms that act like “markers” on genes, controlling their activity
without altering the underlying DNA or RNA sequences.
Traditionally, DNA and RNA epigenetics
have been studied as separate systems. These two mechanisms were thought to
operate independently, each contributing to different stages of the gene
regulation process.
Perhaps that was a mistake.
In a publication in the journal Cell, researchers led by François Fuks, the Laboratory
of Cancer Epigenetics, ULB Faculty of Medicine, ULB-Cancer Research Center, and
Jules Bordet Institute, H.U.B. reveal that in fact, DNA and RNA epigenetics
could be more interconnected than previously thought. The researchers have
discovered that they form a complementary regulation system, in which DNA
epigenetics organizes the available genes and RNA epigenetics dynamically
adjusts their use.
How
Dual Epigenetic Markers Work
In concrete terms, the study
demonstrates that when these two markers are added jointly to a gene, they
enable a more effective activation of that gene. On the other hand, if one of
these processes is not working correctly, the gene’s activity diminishes.
François Fuks and his colleagues have shown that this mechanism is particularly
important in key stages like cells’ development or their specialization into
different types, for example in embryonic stem cells.
This combination offers incredibly
precise regulation of gene activity, essential to the development of organisms
and the harmonious functioning of cells.
Implications for Biology and
Medicine
Published on January 17 in the
journal Cell, this fundamental breakthrough sheds light on a
completely new mode of gene control, opening up unprecedented perspectives in
biology. It helps us to gain a better understanding of how our cells work and
how disruptions to these mechanisms can cause diseases like cancer.
This discovery could also lead to
advances in cancer treatments. Making use of this complementary regulation
system raises the prospect of developing therapies based on “epigenetic drugs”
that target DNA and RNA at the same time. The scientists hope to be able to
develop more precise and personalized treatments, capable of targeting these
regulation mechanisms to restore balance to diseased cells in cancer patients.
Prof. Fuks’ team is already carrying
out research connected directly to the work published in Cell. These ongoing studies aim to demonstrate the
clinical usefulness of their discovery, by exploring the potential of
epigenetic therapies acting on DNA and RNA.
Reference: “Fine-tuning of gene
expression through the Mettl3-Mettl14-Dnmt1 axis controls ESC differentiation”
by Giuseppe Quarto, Andrea Li Greci, Martin Bizet, Audrey Penning, Irina
Primac, Frédéric Murisier, Liliana Garcia-Martinez, Rodrigo L. Borges, Qingzeng
Gao, Pradeep K.R. Cingaram, Emilie Calonne, Bouchra Hassabi, Céline Hubert,
Adèle Herpoel, Pascale Putmans, Frédérique Mies, Jérôme Martin, Louis Van der
Linden, Gaurav Dube, Pankaj Kumar, Romuald Soin, Abhay Kumar, Anurag Misra, Jie
Lan, Morgane Paque, Yogesh K. Gupta, Arnaud Blomme, Pierre Close,
Pierre-Olivier Estève, Elizabeth A. Caine, Kristin M. Riching, Cyril Gueydan,
Danette L. Daniels, Sriharsa Pradhan, Ramin Shiekhattar, Yael David, Lluis
Morey, Jana Jeschke, Rachel Deplus, Evelyne Collignon and François Fuks, 17
January 2025, Cell.
DOI: 10.1016/j.cell.2024.12.009
The work is supported by the F.N.R.S,
Télévie, Welbio, the Belgian Foundation Against Cancer, an ARC (Action de
Recherche Concertée – Collective Research Initiative), the ULB Foundation and
Wallonia.
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