Discover how your experiences and environment influence gene expression without changing your DNA
Explore the ScienceFor decades, we've been captivated by the Human Genome Project. We thought that by mapping every single gene in our DNA, we would unlock the secret to life itself—a master blueprint that dictated our destiny, from our eye color to our disease risk. But a startling revelation emerged: the blueprint wasn't enough. Having the genes was one thing; but how, when, and where they were used was another mystery entirely.
This is where epigenetics enters the stage. Think of your DNA as the script of a play. It contains all the words and stage directions. Epigenetics is the director, the unseen force that tells the actors which lines to deliver, when to deliver them, and with what emotion. This "correspondence" between our fixed genetic code and the dynamic epigenetic controls is rewriting our understanding of biology, revealing how our experiences, environment, and age leave invisible marks on our genes that shape our health in profound ways 1 .
Segments of DNA that carry instructions for building proteins
Chemical modifications that regulate gene activity without changing DNA sequence
Your genes are segments of DNA, the inherited code that carries the instructions for building and maintaining you. Genetics is the study of this heredity—the genes you inherit from your parents. For a long time, this was thought to be the primary, deterministic story of life.
Meaning "above genetics," epigenetics refers to stable, long-term changes that regulate gene activity without altering the underlying DNA sequence 7 . If your genome is the computer's hardware, the epigenome is the software that decides which programs run and when.
The inherited code
Regulate gene expression
The final outcome
Epigenetic control is exerted through several key mechanisms, with the two most prominent being:
This is the process of adding a small chemical tag (a methyl group) directly to a DNA molecule, typically at a spot where a cytosine base is next to a guanine base (a CpG site) 5 . This tag acts like a "do not read" sign, physically blocking the cell's machinery from accessing the gene and effectively silencing it 5 .
DNA is wrapped around proteins called histones, like thread around a spool. These spools can pack together tightly, hiding genes, or loosen up, making genes accessible. Chemical tags—through acetylation, methylation, or phosphorylation—can modify these histones, changing how tightly the DNA is packed 5 .
Genes are inaccessible
High methylation / Low acetylation
Genes are accessible
Low methylation / High acetylation
Selective gene access
Variable modifications
These modifications are influenced by a vast array of factors, from our diet and stress levels to exposure to toxins and UV rays 5 . Furthermore, these patterns change naturally as we age. Recent research mapping DNA methylation in human organs shows that this process becomes less precise over time, leading to changes in gene expression linked to reduced organ function and increased disease susceptibility—providing a clear epigenetic picture of ageing 2 .
For years, DNA methylation and a similar process on RNA (known as the "m6A" mark) were studied as independent, separate systems. But a landmark study published in Cell in January 2025, led by Professor François Fuks and his team, turned this view on its head .
The researchers discovered that these two epigenetic systems are deeply interconnected, forming a complementary partnership for precise gene control. They proposed a "Mettl3-Mettl14-Dnmt1 axis," where the enzymes that mark RNA (Mettl3/Mettl14) directly influence the activity of the key enzyme responsible for DNA methylation (Dnmt1) .
The team used embryonic stem cells (ESCs) as their model system, as these cells undergo rapid changes in gene activity as they specialize. Here's a simplified breakdown of their experimental procedure:
The researchers used tools to deplete or knock out the genes for the RNA-modifying enzymes, Mettl3 and Mettl14, in the ESCs.
They then prompted these genetically altered stem cells to begin differentiating (specializing) into more specific cell types.
Using advanced techniques, the team monitored:
The experiment yielded clear and compelling results, summarized in the table below.
| Experimental Manipulation | Impact on RNA m6A | Impact on DNA Methylation | Impact on Cell Differentiation |
|---|---|---|---|
| Normal Conditions | Normal m6A marks present | Stable DNA methylation patterns | Normal, healthy differentiation |
| Mettl3/Mettl14 Depleted | Drastic loss of m6A marks | Significant reduction in DNA methylation levels | Severe impairment; cells failed to specialize properly |
Source: Adapted from Quarto, G., et al. (2025). Cell.
The analysis showed that when the RNA mark (m6A) was absent, it led to a failure in maintaining DNA methylation. This dual loss disrupted the finely tuned gene expression program required for stem cells to develop, essentially halting the process. The conclusion was that DNA epigenetics acts as the organizer, setting up the available genes, while RNA epigenetics dynamically fine-tunes their use . When both markers are present on a gene, it activates effectively; if one fails, the system breaks down.
| Epigenetic State | Resulting Gene Activity | Biological Outcome |
|---|---|---|
| DNA methylation + RNA m6A present | Effective, precise activation | Successful cell development and specialization |
| Loss of either DNA methylation or RNA m6A | Diminished, dysregulated activity | Failed development; disease states like cancer |
Source: Adapted from Quarto, G., et al. (2025). Cell.
Unraveling these complex mechanisms requires a specialized set of tools. Scientists rely on highly specific research reagents to detect, measure, and manipulate epigenetic marks. The following table details some of the essential items in an epigenetics researcher's toolkit, many of which were pioneered in academic labs like Dr. Or Gozani's at Stanford 7 .
| Reagent / Tool | Function in Research | Example Uses |
|---|---|---|
| DNA Methyltransferases (DNMTs) | Enzymes that add methyl groups to DNA. Used to study the process of methylation. | Enzymatic assays to test drug effects on methylation 5 . |
| Histone Octamers / Nucleosomes | Purified spools of histones with or without DNA wrapped around them. | In vitro binding or enzymatic assays to study how modifications occur 7 . |
| Specific Antibodies | Proteins that bind to a unique target, such as a specific histone modification (e.g., H3K27ac). | Western analysis, immunoprecipitation to detect and purify modified proteins 7 . |
| Purified Recombinant Proteins (e.g., GST-tagged) | Engineered versions of epigenetic enzymes (e.g., SETD6, SIRT1) produced in pure form. | Studying enzyme function, structure, and interactions in a controlled test tube environment 7 . |
| Methyltransferase Assays (e.g., EPIgeneous™) | A universal biochemical test that measures the activity of DNA and histone methyltransferase enzymes. | Screening for potential new epigenetic drugs; studying enzyme kinetics 5 . |
Modern epigenetic research combines these tools with cutting-edge technologies like CRISPR epigenome editing, single-cell sequencing, and computational biology to unravel the complex regulatory networks that control gene expression.
The discovery that DNA and RNA epigenetic systems work in concert is more than a laboratory curiosity; it's a fundamental shift with profound implications. This new understanding helps explain how disruptions in these precise mechanisms can lead to diseases like cancer and offers a roadmap for novel therapies .
The future of medicine may well lie in "epigenetic drugs" that can target both DNA and RNA marking systems simultaneously, potentially restoring healthy gene expression patterns in diseased cells .
As we build huge atlases of how methylation changes with age, we can identify more targets for anti-ageing therapies, moving from simply treating disease to promoting long-term health 2 .
The correspondence between our genes, our environment, and our health is ongoing and dynamic. Epigenetics provides the vocabulary to read this correspondence, reminding us that our genetic destiny is not fixed in stone but is a story still being written, with each mark above our genome a new sentence in the complex narrative of life.